Newswise — NEW YORK, August 5, 2020—The Cancer Research Institute (CRI), a U.S. nonprofit organization dedicated to the discovery and development of powerful immunotherapies for all cancers, awarded more than $30.2 million in research grants and fellowships in the 2020 fiscal year ending June 30, 2020. In total, CRI gave 94 awards that will advance cancer immunology research at 56 institutions in 8 countries. This also includes an unprecedented six-month extension of funding support for 23 postdoctoral fellows in response to the global COVID-19 pandemic.
“While the novel coronavirus has upended all aspects of life across the globe, CRI and our scientists remain committed to fulfilling the promise of cancer immunotherapy,” said Jill O’Donnell-Tormey, Ph.D., CEO and director of scientific affairs at the Cancer Research Institute. “We’re proud to support these brilliant scientists and clinicians, especially our young researchers and future leaders, at a critical time in order to bring the benefits of immunotherapy to more cancer patients.”
The awards, which are funded entirely by individual, foundation, and corporate donors, include:
5 Lloyd J. Old STAR Awards, providing grants of $1.25 million over 5 years to future “stars” in the field of cancer immunology for the exploration of out-of-the-box and disruptive avenues of research
8 Anna-Maria Kellen Clinical Accelerator grants, notably including new cohorts for the PORTER prostate cancer platform study in partnership with the Parker Institute for Cancer Immunotherapy and a circulating tumor DNA study in partnership with the Canadian Cancer Trials Group
32 Irvington Postdoctoral Fellowships, providing $175,500 over three years to further career development and support laboratory research for promising young scientists working under the mentorship of leading immunologists. In addition, CRI has provided sixth-month extensions to 23 Irvington Postdoctoral Fellows whose research has been disrupted by the global COVID-19 pandemic.
12 Clinic and Laboratory Integration Program (CLIP) grants, providing $200,000 in catalytic support for the translation of basic laboratory discoveries into novel therapies that can be tested in patients
5 Technology Impact Awards, supplying seed funding of up to $200,000 to be used over 24 months to address the gap between technology development and clinical application of cancer immunotherapies
9 Impact Grants, including funding for the CRI iAtlas interactive web portal for immuno-oncology research, and a grant to study gliomas, a cancer of the brain stem.
The 2020 Cancer Research Institute Lloyd J. Old STARs, or “Scientists Taking Risks” include:
Joshua D. Brody, M.D., of the Icahn School of Medicine at Mount Sinai, who is refining an approach to therapeutic cancer vaccination, known as in situ vaccination, with the potential to teach patients’ immune systems to recognize tumor cells and target them throughout the body
Tal Danino, Ph.D., of Columbia University, who is leveraging modern approaches from synthetic biology to engineer safe and effective bacterial immunotherapies for cancer
Greg M. Delgoffe, Ph.D., of University of Pittsburgh School of Medicine, who is conducting a deep analysis of the interplay between metabolic stress and immune dysfunction in cancer, and attempting to reprogram cell metabolism to bolster immune responses
Gavin Peter Dunn, M.D., Ph.D., of the Washington University School of Medicine, who is exploring fundamental questions of glioblastoma immunobiology necessary to the development of cancer immunotherapies for the unique anatomy of the central nervous system
Ping-Chih Ho, Ph.D., of the Ludwig Institute for Cancer Research / University of Lausanne, who is deciphering metabolic crosstalk in the tumor microenvironment to unleash cancer-fighting immune cells.
To help advance immunotherapy for two types of ultra-rare cancer, chordoma and fibrolamellar cancer, which affect the bones of the spine and the liver, respectively, the Cancer Research Institute has partnered with two nonprofits focused on these diseases to fund promising research aimed at improving outcomes for patients with these cancers. These include:
The inaugural CRI-Chordoma Foundation CLIP grant, which has been awarded to Cassian Yee, M.D., of the University of Texas MD Anderson Cancer Center to identify immunogenic targets by directly examining the peptides presented on the surface of chordoma cells using tandem mass spectrometry
A CRI-Fibrolamellar Cancer Foundation Postdoctoral Fellowship, which has been awarded to FranciscoJuan Martinez Navarro, Ph.D., in the lab of Sofia de Oliveira, Ph.D., at the Albert Einstein College of Medicine, who is investigating the role of the innate immune system in fibrolamellar hepatocellular carcinoma progression and how it influences the infiltration of T cells into these rare liver tumors.
Among this year’s Technology Impact Award recipients is Neville Sanjana, Ph.D., of the New York Genome Center, who is using massively-parallel genome engineering to comprehensively map all genes that can boost immune responses against pancreatic cancer, which will hopefully enable the development of next-generation T cell therapies for difficult-to-treat cancers.
Finally, included in the Impact Grants is funding for a glioma study carried out by Robert Michael Angelo, M.D., Ph.D., and Sean Bendall, Ph.D., of Stanford University in collaboration with investigators at City of Hope, Stanford, the University of California, Los Angeles, and the University of California, San Francisco, who will use Multiplexed Ion Beam Imaging (MIBI) to image intact, well-annotated glial tumor tissue from pediatric and adult patients in response to vaccine, checkpoint inhibitor, and cellular therapies. This dataset will inform therapeutic strategies based on the presence of tumor targets, expression of immune inhibitory proteins, and the types and functional statuses of T cells and myeloid cells within the context of an intact tumor microenvironment.
About the Cancer Research InstituteThe Cancer Research Institute (CRI), established in 1953, is a highly-rated U.S. nonprofit organization dedicated exclusively to saving more lives by fueling the discovery and development of powerful immunotherapies for all cancers. Guided by a world-renowned Scientific Advisory Council that includes four Nobel laureates and 26 members of the National Academy of Sciences, CRI has invested $445 million in support of research conducted by immunologists and tumor immunologists at the world’s leading medical centers and universities, and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. To learn more, go to cancerresearch.org.
Immune checkpoint inhibitors such as Roche’s Tecentriq and Merck & Co.’s Keytruda have shown efficacy in triple-negative breast cancer, but their anti-tumor activity in the HER2-positive subtype remains limited.
Now scientists at Duke University have demonstrated that priming the immune system with a vaccine boosts the activity of existing PD-1/L1 checkpoint inhibitors in mouse models of HER2-positive breast cancer. Combining a vaccine targeting an oncogenic variant of HER2 that lacks exon 16 (HER2D16) with an anti-PD-1 antibody cleared tumors in the mice and led to prolonged survival, according to results published in the journal Clinical Cancer Research.
The promising results have led to a phase 2 clinical trial that’s testing a similar HER2 vaccine, called VRP-HER2, in combination with Keytruda in patients with advanced HER2-overexpressing breast cancer.
Unlike triple-negative breast cancer, HER2 breast cancer generally contains fewer antigenic elements that the immune system can recognize and fewer tumor-infiltrating T cells. That partly explains why unleashing the full power of the immune system with a PD-1/L1 blocker still doesn’t work well in this subtype of cancer.
Using patient samples, the Duke team confirmed that HER2D16 expression can impede HER2-targeting therapies, including Roche’s Herceptin and Kadcyla. Therefore HER2D16 may represent an important signaling mechanism that causes HER2-positive tumors to resist drug therapies, making it a good target for immunotherapy, they argued.
The team designed an adenovirus-vectored vaccine against HER2D16. In mice, a single vaccination triggered strong HER2-specific T-cell and antibody responses, which slowed tumor growth. However, the vaccine by itself couldn’t eradicate the tumors. The researchers suggested that the PD-1/L1 immunosuppressive mechanism was to blame, leading them to test a combination of the vaccine and an anti-PD-1 attack.
“The basic premise is that the immune checkpoint inhibitors work fantastic if the body has already triggered an immune response, but they don’t work well in the absence of that,” Kim Lyerly, an author of the study, explained in a statement.
While HER2-positive breast cancer didn’t respond to solo PD-1 in a mouse model, the combo achieved significant improvement in survival, with about 30% of mice experiencing complete tumor regression and more than 150 days of long-term tumor-free survival, the team reported. Further analysis revealed that the vaccination not only induced systemic immune responses, but also enhanced HER2-specific CD8 T cells that infiltrate into tumors.
There has been increased interest in cancer vaccines, which aim to trigger an immune response against cancer. Scientists at the National Cancer Institute genetically modified dendritic cells from patients to produce parts of the HER2 protein as a vaccine.
A team at Arizona State University focused on frameshift peptides, which are proteins produced when errors occur during genetic information transfer from DNA to RNA in cancer cells. Breast cancer was one type that had large amounts of the peptides for potential vaccine design, the team found.
The Duke University scientists believe their study showed that a vaccine targeting HER2D16 is effective in eliciting antitumor T-cell responses, which can be further improved by an PD-1 inhibitor. A phase 2 trial is already testing the findings in humans with HER2-positive breast cancer. Although the current study has only examined the combo approach in breast cancer, future studies could include other HER2-positive cancer types such as gastric cancer, or even target other oncogenes, the researchers wrote in the study.
“Fucoidan is a natural sulphated polysaccharide that exists mainly in the cell wall matrix of various species of brown seaweed.
“The brown seaweeds containing fucoidan are widely consumed as part of the normal diet in East Asia, particularly Japan, China and Korea.
“Fucoidan mediates its activity through various mechanisms such as induction of cell cycle arrest, apoptosis and immune system activation.
“Additional activities of fucoidan have been reported that may be linked to the observed anti-cancer properties and these include induction of inflammation through the immune system, oxidative stress and stem cell mobilization.”
Pothuri reports grants, personal fees and nonfinancial support outside the submitted work, including for serving as the principal investigator for industry sponsored trials, from AstraZeneca, Clovis Oncology, Genentech, GlaxoSmithKline, Merck, Roche and Tesaro; as well as advisory board roles with AstraZeneca, Eisai, GlaxoSmithKline and Tesaro. Please see the study for all authors’ relevant financial disclosures.
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Women who underwent chemotherapy or surgery for gynecologic cancer and also had COVID-19 infection did not appear at significantly increased risk for death due to the novel coronavirus, according to study findings published in Cancer.
However, recent immunotherapy use appeared associated with increased risk for COVID 19-related mortality, researchers noted.
“Initial reports out of China that showed increased severity and risk for death associated with COVID-19 among patients undergoing cancer therapy and surgery were based on very small numbers of patients with cancer,” Bhavana Pothuri, MD, MS, professor in the department of obstetrics and gynecology at NYU Langone’s Perlmutter Cancer Center, told Healio. “In addition, very few women with gynecologic cancer were included in the studies and we noticed very different observations clinically, which is why we worked with our collaborators at other NYC institutions to report outcomes of a diverse group of gynecologic oncology patients.”
Pothuri and colleagues pooled data on demographics and clinical outcomes of 121 women (median age at diagnosis, 64 years; interquartile range, 51-73) with gynecologic cancer who had been diagnosed with COVID-19 infection between March 1 and April 22 and received treatment across six New York City-area hospitals.
Most women (62.7%) had advanced-stage cancer. The most common cancer types included high-grade serous ovarian, fallopian tube or primary peritoneal cancer (27.3%), low-grade endometrial carcinoma (21.5%), high-grade endometrial carcinoma (18.2%) and cervical carcinoma (10.7%).
Results showed an overall mortality rate of 14%. More than half of women (54.5%, n = 66) required hospitalization, and among them 45 (68.2%) required respiratory intervention, 20 (30.3%) were admitted to the ICU and nine (13.6%) underwent invasive mechanical ventilation. None of the women who required mechanical ventilation survived.
Factors associated with hospitalization included age older than 64 years (RR = 2.22; 95% CI, 1.29-3.81); Black race (RR = 2.22; 95% CI, 1.22-4.06); and having three or more comorbidities, including hypertension, diabetes and obesity (RR = 2.01; 95% CI, 1.17-3.44).
Three-quarters (75%) of women had a mild form of COVID-19 infection and recovered, researchers noted.
Late-stage gynecologic cancer, receipt of high-dose chemotherapy and recent major surgery did not appear predictive of COVID-19 severity or death. Conversely, recent immunotherapy use appeared associated with a nearly threefold increased risk for death due to COVID-19 (RR = 2.93; 95% CI, 1.05-8.17), which Pothuri said surprised researchers.
“We were expecting immunotherapy to be protective, as it boosts the immune system, but perhaps it adds to the cytokine release storm with COVID-19,” she said.
However, Pothuri noted the small number of women on immunotherapy, which explains the wide confidence interval, and said this observation needs to be confirmed in a larger cohort.
“Given that we did not find any association of worse COVID-19 outcomes in patients who received chemotherapy or surgery, the most important takeaway is that patients should seek care for their gynecologic cancer regardless of the pandemic — especially since the pandemic seems to be increasing and will likely continue into 2022,” Pothuri said. “Patients should not only continue to receive their screening and preventative measures, but also continue with active therapy for cancer, such as surgery and cancer treatments, to optimize their cancer outcomes.
For more information:
Bhavana Pothuri, MD, can be reached at NYU Langone Health, 240 E. 38th St., 19th Floor, New York, NY 10016; email: firstname.lastname@example.org.
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THURSDAY, July 30, 2020 (HealthDay News) — Despite rampant fears that cancer patients are at higher risk of having severe cases of COVID-19, a new study suggests gynecologic cancers do not boost the chances of hospitalization or death.
“Our study should be reassuring for women with gynecologic cancers who are worried that having cancer increases their risk of becoming seriously ill if they go to the hospital because of COVID-19,” said lead investigator Olivia Lara, an oncology fellow at NYU Langone’s Perlmutter Cancer Center.
For the study, Lara’s team reviewed the medical records of 121 women, aged 51 to 63, being treated simultaneously for gynecologic cancers and COVID-19 in New York City between March and April.
The results, published online July 31 in the journal Cancer, revealed that these women had similar hospitalization rates and death as those who only had COVID-19.
More than half of the study patients required hospitalization, and among those hospitalized one-quarter died, amounting to a 14% death rate.
The death rate among this sample is comparable to the 21% death rate identified in another study, which included 5,700 hospitalized COVID-19 patients in the city, the study authors noted.
The study could potentially alter the theory that cancer patients face worse odds when infected with COVID-19.
A full 75% of the women with gynecological cancer experienced only a mild form of the disease, according to the report.
The women’s risk of dying from COVID-19 did not increase even if they had late-stage cancer, cancer surgery or high-dose chemotherapy, the study authors said in a New York University news release.
Still, one risk factor related to cancer treatment seemed to increase the odds of death.
Women receiving immunotherapy — treatment that uses a person’s own immune system to fight cancer — were three times more likely to die than women who received standard cancer treatments such as radiation, surgery or chemotherapy.
But only eight out of the 121 participants included in the study were treated with immunotherapy, prompting the study authors to stress that the sample was too small to make any conclusions based on this finding.
The results do underscore the importance of receiving cancer screenings and treatments, despite COVID-19 fears.
“The basic rules of cancer care have not changed during the pandemic,” study senior investigator Dr. Bhavana Pothuri said in the news release. “Early detection, screening and care lead to more people surviving what remains a leading cause of death among American women.”
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The immune system is how the body fights infection and disease. However, cancer cells are sneaky and have evolved over time to effectively hide from and confuse the immune system. To combat this, immunotherapies have been developed that help the body’s immune system to better prevent, control and eliminate cancer.
Some boost the immune system’s activity using cytokines – like interleukins and interferons – which are proteins secreted by the immune system that act as chemical messengers; these are known as immune system modulators.
Others rely on monoclonal antibodies that flag proteins, or antigens, on the outside of cancer cells as invaders, and so recruit other immune cells to destroy any cells with those antigens. These monoclonal antibody drugs also often act as checkpoint inhibitors to release molecular brakes, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), that stop immune cells attacking cancer cells. Checkpoint inhibitors – such as Yervoy and Keytruda – have shown impressive improvement in disease outcome in certain cancer patients to date.
Vaccines, including the Bacille Calmette-Guérin (BCG) for tuberculosis, are also used to help the immune system fight cancer.
In addition, cell-based immunotherapies supplement the immune system with better immune cells, usually through bone marrow transplants or engineering of people’s own T-cells, which is known as CAR-T therapy. Viruses can also be modified to infect cancer cells, so they attract the attention of the immune system.
Unfortunately, despite having promise against all tumour types, their success has been limited. Researchers are working hard to find ways to continue to innovate so all cancer patients can really benefit from this therapeutic approach. To understand the bright future of immunotherapies, it is crucial to look back at progress to date.
130-200 AD – Early expression of role of the immune system in combatting cancer
During Ancient Egyptian times, there were numerous accounts of tumours disappearing or regressing following infection with a fever. This led Greek physician, Claudius Galen (130-200 AD), to write for the first time that cancer might evolve from inflammatory lesions – it is from Galen that we derive the word oncology as he used the Greek work for swelling, oncos, to describe tumours.
1868 – 1882 – First experiments of immune system’s modulation in cancer
After noticing that erysipelas infections in cancer patients led to tumour regression, two German physicians, F Fehleisen and W Busch, intentionally infected cancer patients with this bacterial disease and observed that this caused a noticeable shrinkage of their tumours. Thereby, suggesting that the immune system had a modulatory role in treating cancer. Fehleisen then figured out which bacteria causes erysipelas, Streptococcus pyogenes.
1891-9 – First immunotherapy developed by Coley
New York surgeon William B Coley also noticed that after an erysipelas infection his sarcoma patients saw a long-term tumour regression Other case reports showed patients experienced spontaneous remission after an acute bacterial infection, so he began a 40-year project where he injected mixtures of live and inactivated Streptococcus pyogenes and Serratia marcescens bacteria, known as ‘Coley’s toxins’ into patients with inoperable tumours.
He reported that more than 1,000 patients had experienced remission and been cured of cancer. This is often viewed as the first immune-based treatment for cancer and has earnt Coley the title of ‘Father of Immunotherapy’.
Viruses also emerged as a potential trigger for immune responses against tumours; in 1896, American doctor George Dock documented tumour remission following a severe influenza infection in leukaemia patient.
1940s-1960s – Discovery that tumours have specific antigens
Following on from Paul Ehrlich’s work on antibodies and how they combine with antigens in the late 1800s, scientists carried out research into tumours removed from animals. These studies discovered “tumour-associated antigens” (TAAs), which the immune system could potentially recognise and form the basis of therapies. In the 1950s, researchers began to search for targetable TAAs and antibodies that can could bind to them.
This occurred in the context of hesitancy and scepticism in the medical community about the use of immunotherapies, because there was a lack of understanding about their mechanism of action; instead chemotherapies, which started to be approved in the 1940s, became the preferred choice, alongside the traditional surgical approach.
1940s-1960s – Discovery of interferon
In 1957, the interferon – a cytokine produced by white blood cells – was discovered; there is dispute about the scientists who should be credited. It was initially viewed as useful against viruses, but over the next few years, various researchers found it to also be effective against cancer in mice models.
1950s-1970s – BCG’s promise in cancer
The idea of using bacterial infections as effective approach against cancer re-emerged in the 1950s when Lloyd Old and his team carried out a study that showed the anti-tumour effects of tuberculosis-related BCG bacteria in mice with bladder cancer. In the 1970s, further studies were carried out into the promise of this bacteria in melanoma remission.
The BCG vaccine was approved by the US Food and Drug Administration (FDA) in 1990 for bladder cancer; it remains the standard of care in that indication to this day.
1970s – Promise of interleukins emerges
While seeking to grow T cells in a culture, Robert Gallo and his team at the US National Institutes of Health’s Intramural Research Program identified the cytokine, T-cell growth factor, which is now known as interleukin-2 (IL-2). This allowed researchers to better study the immunology of T cells, as well as provided a direct way to ramp up a weak host immune response to cancer.
1986 – FDA approval of first immunotherapy, interferon-alpha 2
Following on from earlier work in the 1950s and 1960s in identifying interferon’s promise in cancer, the first immunotherapy agent that targets interferon-alpha 2 was approved by the US FDA in 1986. Its initial indication was hairy cell leukaemia, but within a decade it was also approved for Stage IIb/III melanoma.
1990s – Birth of checkpoint inhibitors
Following the success of cytokine-based immunotherapies and BCG vaccines, scientists began to look even wider for ways to use the immune system against tumours.
They built upon research in 1987 by Jean-François Brunet where he identified the first immune checkpoint molecule, CTLA-4. However, it wasn’t until 1995 when the University of California, San Francisco’s Dr James Allison suggested that blocking CTLA-4 would enhance the activation of T cell responses in cancer. Next came the discovery of the PD-1 in 1992 by Tasuku Honjo at Kyoto University in Japan.
2002 – CAR-T technology developed
Research by Dr Allison in the 1980s had led to better understanding of how T cells work and how they can be used in cancer treatment. However, Memorial Sloane Kettering Cancer Center researchers Michel Sadelain, Renier Brentjens, and Isabelle Rivière took this one step forward by genetically engineering T cells with a chimeric antigen receptor (CAR).
These so-called CAR-T cells are engineered so they target T lymphocytes to antigens on the surface of tumours, thereby creating a new immunotherapy method.
2011 – First checkpoint inhibitor approved, enter Bristol Myers Squibb’s Yervoy
Bristol Myers Squibb (BMS) became the first company to have a checkpoint inhibitor approved. Yervoy (ipilimumab) is a monoclonal antibody that targets CTLA-4 and turns off the inhibitory mechanism of cytotoxic T lymphocytes, so they can effectively recognise and destroy cancer cells. It was initially approved for melanoma but is now available for colorectal cancer and hepatocellular carcinoma, among others.
Yervoy was followed in 2015 by Merck and Keytruda (pembrolizumab). Instead of targeting CTLA-4, Keytruda targets another checkpoint, PD-1. Keytruda is now of the world’s most well-known drugs; it has been approved for 17 oncology indications to date.
2015 – First oncolytic virus therapy approved in the west
The use of naturally occurring viruses to treat disease had largely been abandoned in the 1970s, however, researchers began to experiment with using novel technology to engineer viruses to improve their ability to induce an immune response against cancer cells. This therapeutic approach is called oncolytic virus therapy.
The Herpes Simplex virus type 1 (HSV-1) emerged as an early candidate for cancer immunotherapies. In 2015, the FDA approved BioVex’s T-VEC (talimogene laherparepvec) for melanoma; T-VEC is made from an HSV-1 genetically modified to express human granulocyte-macrophage colony-stimulating factor (GM-CSF). This encouraged the virus to target tumour cells, replicate inside them and induce immunologic responses at the tumour sites.
To date, this is the only oncolytic virus therapy approved by the FDA, but hundreds of others are in clinical trials for a range of cancers.
2017 – Kymriah becomes first approved CAR-T therapy
A huge medical breakthrough was made in 2017 when Novartis’s CAR-T therapy Kymriah (tisagenlecleucel) was approved by the FDA for patients under 25 with refractory or relapsed B-cell precursor acute lymphoblastic leukaemia. It is a genetically modified, personalised autologous T cell immunotherapy targeted CD19. Since Kymriah has also been approved for diffuse large B-cell lymphoma, a common form of non-Hodgkin lymphoma.
It was followed one year later by Gilead’s Yescarta (axicabtagene ciloleucel), which similarly targets CD19, but is approved for adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Both of these therapies are now widely available globally, including in the UK through the NHS.
Challenges remain however, as they are only available to certain late-stage blood cancer patients and producing CAR-T therapies for solid tumours still poses problems for researchers.
In addition, since they are so expensive – more than $400,000 per patient – only a small number of patients who actually have the right cancer type have been treated to date.
2010s – Combining checkpoint inhibitors
Although checkpoint inhibitors have revolutionised the oncology space, many patients still don’t demonstrate durable long-term responses and are impacted by immune-related adverse events. Checkpoint inhibitors may not be as toxic chemotherapy, but these side effects are still concerning.
To improve their efficacy and safety in more patients, researchers have started to combine checkpoint inhibitors. This builds on long-standing approaches of combining immunotherapies with chemotherapy. Cancer cells often employ multiple mechanisms to evade the immune system, meaning more than one approach is needed to combat that.
In 2015, the FDA approved the first combination immunotherapy, Yervoy and BMS’ PD-1 inhibitor, Opdivo (nivolumab) for advanced melanoma.
2020 – Further improving checkpoint inhibitors through drug delivery
A further attempt to improve checkpoint inhibitors involves converting so-called ‘cold’ tumours, which can still evade the immune system, into ‘hot’ ones. Cold tumours are particularly a problem in breast, ovarian, prostate, and pancreatic cancers, leaving these patients ineligible for checkpoint inhibitors.
Researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) have come up with a drug delivery solution; the research was published in Nature Biomedical Engineeringin mid-April.
Their solution leverages the cytokine IL-12, which is known to turn cold tumours hot, but has serious toxicity issues. Therefore, the research team, led by Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering, developed a drug delivery system that attaches IL-2 to a blood protein, which binds to collagen in areas of vascular injury, including in tumours themselves. The IL-12 collagen combination was then used alongside checkpoint inhibitors.
Delivering IL-12 directly to tumours, reduced its toxicity by two-thirds and researchers saw cancer disappear after treatment in mouse models with aggressive forms of breast cancer.
The next stage is to study IL-12 in tumours elsewhere in the body, with eventual aim of progressing into clinical trial.
The two-year agreement is to focus on the microbiome’s role in chemotherapy, specifically its influence on its effectiveness and how response rates can be improved by decreasing gut inflammation.
“This is a perfect fit for such a project with Prof. Martin Blaser’s extensive knowledge of the microbiome and its complex interactions with human physiology and more particularly with the human immune system,” says Sébastien Guéry, HMV leader at DuPont Nutrition & Biosciences.
“HMV was launched in 2017 to spearhead the development of next generation microbiome solutions for improved health and wellness.
“We believe there is a high unmet medical need to improve the quality of care of patients undergoing chemotherapy and potentially improve the benefit/risk ratio of such interventions.”
The agreement is set to use insights garnered from previous work that demonstrate that oral intake of oncology drugs can induce enterocolitis, a condition that causes inflammation of the digestive tract.
The condition specifically affects the inner linings of both the small intestine and the colon, causing several symptoms that include vomiting and diarrhoea amongst others.
With the increasing use of multiple, new and aggressive chemotherapeutic agents for a number of tumour types, the prospect of increased cases of enterocolitis is all too real.
As such, the agreement takes the view that administration of beneficial microbes may lead to improving overall patient care and comfort while undergoing cancer treatment.
Improving cancer therapies
“We are delighted to further develop our relationship with DuPont for the benefit of human health,” says Martin Blaser, director of the Center for Advanced Biotechnology and Medicine.
“The interaction of the microbiome with cancer is an important frontier, with important leads already. Our project is aimed to discover new ways to improve cancer therapies.”
While much of this research takes place in academic circles, industry has taken a keen interest in the microbiome’s role in cancer particularly as latest figures suggest a rise in cases, driven by more people living to an older age and lifestyle changes occurring in the developing world.
Companies active in this space includes US-based Vedanta Biosciences, which last year isolated 11 bacterial strains from healthy human donor faeces in order to investigate their ability to enhance antimicrobial or antitumour immunity in mouse models.
Closer to home UK-based 4D Pharma, a pharmaceutical company currently investigating the effects of its live biotherapeutic MRx0518.
The candidate contains a proprietary strain of the Enterococcus bacterium species, which may have anti-cancer and immune system modulating effects in patients, who have undergone the removal of solid tumours.
In January this year, 4D pharma also teamed up with academia, this time with the University of Texas MD Anderson Cancer to conduct a study evaluating MRx0518’s efficacy in patients with resectable pancreatic cancer.
Other firms active in this research area include Israeli-based BiomX, which is developing both natural and engineered phage therapies that target bacteria naturally present in tumours.
The aim is to convert these ‘cold’ tumours to ‘hot’ by releasing an immunostimulatory ‘payload’ and eradicate bacteria such as Fusobacterium nucleatum that appear to protect the tumour.
“Using synthetic biology, we can create phage therapies that exploit the co-existence of specific bacteria within cancerous tumours to induce a focused anti-tumour immune response,” explains Jonathan Solomon, BiomX’s CEO.
“Moreover, these phage therapies will potentially boost the effect of immunotherapies, which are spearheading the future of cancer treatment.
“These results show early promise for our colorectal cancer program and for future targeting of bacteria in additional cancer types.”
The global burden of cancer is growing and a wide disparity in the incidence, malignancy and mortality of different types of cancer between each sex has been demonstrated. The sex specificity of cancer appears to be a relevant issue in the management of the disease, and studies investigating the role of sex and gender are becoming extremely urgent. Sex hormones are presumably the leading actors of sex differences in cancer, especially estrogens. They modulate gene expression, alter molecules and generate disparities in effectiveness and side effects of anticancer therapies. Recently immunotherapy aims to improve anticancer treatment strategies reducing off-target effects of chemotherapy and direct cancer cells killing. It is recognized as a fruitful strategy to treat and possible to cure cancer. Immunotherapeutic agents are used to activate or boost the activation of the immune system to fight cancer cells through physiological mechanisms often evaded in the offensive march of the disease. These therapeutic strategies have allowed new successes, but also have serious adverse effects including non-specific inflammation and autoimmunity. Sex and gender issues are of primary importance in this field, due to their recognized role in inflammation, immunity and cancer, and the clarification and understanding of these aspects is a necessary step to increase the responses and to diminish the adverse effects of immunotherapy. This review describes the available knowledge on the role of sex and gender in cancer immunotherapy, and will offer insights to stimulate the attention and practice of clinicians and researchers in a gender perspective of new cancer treatment strategies.
Something has been eating at us: how few folks understand that their food choices have a huge impact on their risk of various cancers — head and neck, esophageal, colon, stomach, lung, breast, pancreatic and prostate cancers — and the impact that foods can have on cancer treatment’s effectiveness. Did you know:
– Studies on the effects of food on your health indicate that various phytochemicals in fruits, vegetables and grains nurture your good-for-you gut microbes, which in turn decrease your cancer risk. They do it by boosting or protecting your cellular metabolism, immune system and the function of every organ in your body. How you feed your gut bacteria may also have far-reaching effects on the outcome of chemotherapy and cancer drugs by affecting everything from insulin levels to cancer-promoting amino acids, according to several lab studies.
– Folks who eat a variety of foods and drinks that are rich in the 6,000 different anti-inflammatory and immune-boosting phytonutrients called flavonoids slash their cancer risk.
– Women who eat the least red meat have a 23% lower risk of developing invasive breast cancer than women who eat the most red meat.
– Not eating enough whole grains and eating processed meats are two major causes of cancer in America.
That’s pretty riveting info. So let’s take a deeper dive into how you can take a bite out of cancer every time you take a bite of food and a gulp of a beverage. Here are the phytonutrients and foods you want on your menu:
Flavonoids: They’re found in many vegetables, fruits, herbs and spices, and green and black tea. You want to take in a wide variety of at least 500 milligrams of flavonoids daily, the level that provides the best protection against cancer, according to a 23-years-long study published in Nature Communications. You can do that by enjoying one cup of tea, one apple, one orange, 3 ounces of blueberries, and 3 ounces of broccoli.
You want a variety because a major review published in the journal Antioxidants found that different types of flavonoids are associated with a decreased of the risk of different types of cancer:
– Catechin found in berries, apples and apricots and flavonols in onions, leeks, Brussels sprouts, kale, broccoli, tea, berries, beans and apples for prostate cancer.
– Epicatechin in green tea, grapes and cocoa for breast cancer.
– Proanthocyanidins in grape skin, cranberry and green tea for lung cancer.
– Flavones in celery, parsley, various herbs and hot peppers for colorectal cancer.
– And total flavonoids for gastric cancer.
Fiber: Digestible and nondigestible fiber found in 100% whole grains, fruits and vegetables feeds your good gut bacteria and protects your gastrointestinal tract, and it’s instrumental in the fight against colorectal and breast cancer. If you enjoy seven to nine servings daily of fruits and veggies, and eat two servings of whole grains a day you will be getting the fiber you need.
Cruciferous vegetables: Broccoli, cauliflower, turnips, collard greens, cabbage, Brussels sprouts, bok choy, arugula, horseradish, radish, watercress and kale are tasty examples. Certain ones have been associated with a reduced risk of breast, head and neck, esophageal and stomach cancers and with boosting resistance to lung and colorectal cancers. You can aim to eat at least two servings a day — say, an arugula salad (around 2 cups in a serving) and a side of roasted turnips (1 cup per serving).
Lycopene: It’s a carotenoid (a building block of vitamin A) that’s found in tomatoes and is especially bioavailable when tomatoes are cooked. It is also found in pink grapefruit, watermelon and apricots. Lycopene is associated with reduced risk of aggressive prostate and gastrointestinal cancers as well as reducing the activity of lung cancer cells in the lab. Studies indicate that 8-21 mg daily may offer the most benefit — that’s about 3 ounces of watermelon (4.5 mg), 1.5 ounces of tomato puree (11 mg) and 3 ounces of guava (5.3 mg).
Mehmet Oz, M.D. is host of “The Dr. Oz Show,” and Mike Roizen, M.D. is Chief Wellness Officer and Chair of Wellness Institute at Cleveland Clinic. To live your healthiest, tune into “The Dr. Oz Show” or visit sharecare.com.
Women with breast cancer who have also experienced a heart attack or other cardiac event are 60% more likely to die of the disease, a new study has revealed.
While previous research had shown that breast cancer patients are more likely to develop heart disease thanks to the toxic effects of chemotherapy and radiation on cellular health, this study is the first to establish a correlation between heart attacks and an increased risk of mortality from breast cancer, which one in eight American women will develop in their lifetime.
A team of researchers led by Graeme Koelwyn, PhD, of New York University Robert I. Grossman School of Medicine found that of 1,700 women with early-stage breast cancer, those who experienced heart failure or a stroke or heart attack often had worse outcomes—recurrence, metastasis, death—than those who did not.
How might cardiovascular disease hasten the progression of breast cancer? The researchers point to an animal study that demonstrated that heart attacks trigger an immune cell-crippling autoimmune reaction, allowing cancer to spread unchecked throughout the body.
“By blunting the immune system’s assault on cancer cells, a heart attack appears to provide an environment that enables tumor growth,” said coauthor Kathryn Moore, PhD, director of the cardiovascular research center at NYU Langone Health, though she cautions that further study of the relationship between cardiovascular disease and cancer is needed.
To induce nondeadly heart attacks in mice that had had cancer cells implanted in their breast tissue, the researchers “ligated,” or limited the blood flow to, their coronary arteries. Subsequent testing revealed a marked increase in the size of tumors that sported surface markers associated with rapid proliferation; a decrease in the function of immature monocytes, a type of white blood cell that can be found in the bone marrow and the bloodstream as well as in tumors; and changes in the expression of genes and proteins linked to the production of a heightened immune response. These effects were not seen in mice that had cancer but had normal blood flow to the coronary arteries, meaning that they could be safely attributed to the reduced cardiovascular function caused by the operation.
Published in Nature Medicine last week, the results could potentially change the way breast cancer is treated, according to Koelwyn. “Given the evidence of cross-talk between cardiovascular disease and breast cancer,” he said, “measures that lower the risk for a cardiovascular event, such as exercise and treating high cholesterol and high blood pressure, warrant further study as potential ways to keep patients’ cancer from getting worse.”
For more on the connection between heart health and cancer, click here.