Prebiotics may help activate anti-tumor immunity

Prebiotics may help activate anti-tumor immunity

Scientists at Sanford Burnham Prebys Medical Discovery Institute have shown that two prebiotics, mucin and inulin, slowed the growth of melanoma in mice by boosting the immune system’s ability to fight cancer. In contrast to probiotics, which are live bacterial strains, prebiotics are “food” for bacteria and stimulate the growth of diverse beneficial populations. The study, published today in Cell Reports, provides further evidence that gut microbes have a role in shaping the immune response to cancer, and supports efforts to target the gut microbiome to enhance the efficacy of cancer therapy.

#inulin #prebiotics #cancer

Prebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth

Yan Li, Lisa Elme´ n, Igor Segota, Tao Long, Scott N. Peterson, Ze’ev A. Ronai

https://doi.org/10.1016/j.celrep.2020.01.035

https://www.sciencedirect.com/science/article/pii/S2211124720300504#app2

Creatine powers the immune system to fight cancer

Creatine powers the immune system to fight cancer

Creatine powers the immune system to fight cancer

The energy-buffering function of creatine certainly goes beyond regulating CD8 T cells. In CrT-KO mice, we have observed the hyporesponsiveness of multiple immune cells in various mouse tumor models. It is also likely that creatine regulates immune reactions to multiple diseases beyond cancer, such as infections and autoimmune diseases (Riesberg et al., 2016). Studying the roles of creatine in modulating various immune cells under different health and disease conditions will be interesting topics for future research.

Stefano Di Biase, Xiaoya Ma, Xi Wang, Jiaji Yu, Yu-Chen Wang, Drake J. Smith, Yang Zhou, Zhe Li, Yu Jeong Kim, Nicole Clarke, Angela To, Lili Yang. Creatine uptake regulates CD8 T cell antitumor immunity. The Journal of Experimental Medicine, 2019; jem.20182044 DOI: 10.1084/jem.20182044

#creatine #tumors #cancer

http://jem.rupress.org/content/early/2019/10/17/jem.20182044/tab-metrics

Virus kills melanoma in animal model, spares normal cells

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Researchers from Yale University School of Medicine have demonstrated that vesicular stomatitis virus (VSV) is highly competent at finding, infecting, and killing  human melanoma cells, both in vitro and in animal models, while having little propensity to infect non-cancerous cells.

“If it works as well in humans, this could confer a substantial benefit on patients afflicted with this deadly disease,” says Anthony van den Pol, a researcher on the study. The research was published online ahead of print in the Journal of Virology.

Most normal cells resist virus infection by activating antiviral processes that protect nearby cells. “The working hypothesis was that since many cancer cells show a deficient ability to withstand virus infection, maybe a fast-acting virus such as VSV would be able to infect and kill cancer cells before the virus was eliminated by the immune system,” says van den Pol. And indeed, the virus was able to selectively infect multiple deadly human melanomas that had been implanted in a mouse model, yet showed little infectivity towards normal mouse cells, he says.

Many different mechanisms are involved in innate immunity, the type of immunity that combats viral infection. van den Pol plans to investigate which specific mechanisms are malfunctioning in cancer cells, knowledge that would be hugely beneficial both in understanding how cancer affects immunity, and in enhancing a virus’ ability to target cancer cells, he says.

Melanoma is the most deadly skin cancer. Most melanomas are incurable once they have metastasized into the body. The incidence of melanoma has tripled over the last three decades, and it accounts for approximately 75 percent of skin cancer-related deaths.

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A copy of the manuscript can be found online at http://bit.ly/asmtip0413b.  Formal publication is scheduled for the June 2013 issue of the Journal of Virology.

(G. Wollmann, J.N. Davis, M.W. Bosenberg, and A.N. van den Pol, 2013. Vesicular stomatitis virus variants selectively infect and kill human melanomas but not normal melanocytes. J. Virol.  Published ahead of print 3 April 2013 , doi:10.1128/JVI.03311-12)

Journal of Virology is a publication of the American Society for Microbiology (ASM).  The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

Naturally-occurring substance proves effective against deadly skin cancer in laboratory tests

Contact: Joseph Carey jcarey@txbiomed.org 210-258-9437 Texas Biomedical Research Institute

For the first time, scientists have demonstrated the mechanism of action of gossypin, a naturally-occurring substance found in fruits and vegetables, as a treatment for melanoma, which causes the majority of deaths from skin cancer.

“We identified gossypin as a novel agent with dual inhibitory activity towards two common mutations that are the ideal targets for melanoma treatment,” said Texas Biomed’s Hareesh Nair, Ph.D.

At the moment, there is no single therapeutic agent or combination regimen available to treat all melanomas, of which about 76,000 new cases are diagnosed annually, according to the American Cancer Society.

“Our results indicate that gossypin may have great therapeutic potential as a dual inhibitor of mutations called BRAFV600E kinase and CDK4, which occur in the vast majority of melanoma patients. They open a new avenue for the generation of a novel class of compounds for the treatment of melanoma,” Nair added.

His report, appearing in the March 29, 2013 issue of the journal Molecular Cancer Therapeutics, was funded by the Texas Biomedical Forum and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.

Nair and his colleagues found that gossypin inhibited human melanoma cell proliferation, in vitro, in melanoma cell lines that harbor the two mutations. Gossypin stunted activities of the mutated genes, possibly through direct binding with them. It also inhibited the growth of various human melanoma cells. In addition, gossypin treatment for 10 days of human melanoma cell tumors with the mutations transplanted into mice reduced tumor volume and increased survival rate.

Further studies are planned by Nair’s team to understand how the body absorbs gossypin and how it is metabolized. This idea has been discussed with the Cancer Therapy & Research Center at the UT Health Science Center San Antonio’s Deva Mahalingam, M.D, Ph.D., who is interested in testing gossypin in melanoma patients.

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Co-authors on the paper include John L. VandeBerg, Ph.D., and Shylesh Bhaskaran, Ph.D., of Texas Biomed; Kalarikkal V. Dileep, M.Sc., and Chittalakkottu Sadasivan, Ph.D., of Kannur University, in Palayad, India; Deepa S. Sathyaseelan, Ph.D., of the Barshop Institute for Longevity and Aging Studies at the UT Health Science Center San Antonio; Mitch Klausner, Ph.D., of the MatTek Corporation; and Naveen K. Krishnegowda, M.D., and Rajeshwar R. Tekmal, Ph.D., of the Department of Obstetrics and Gynecology at the UT Health Science Center San Antonio.

Texas Biomed, formerly the Southwest Foundation for Biomedical Research, is one of the world’s leading independent biomedical research institutions dedicated to advancing health worldwide through innovative biomedical research.  Located on a 200-acre campus on the northwest side of San Antonio, Texas Biomed partners with hundreds of researchers and institutions around the world, targeting advances in the fight against AIDS, hepatitis, malaria, parasitic infections and a host of other infectious diseases, as well as cardiovascular disease, diabetes, obesity, cancer, psychiatric disorders, and problems of pregnancy.  For more information on Texas Biomed, go to http://www.TxBiomed.org, or call Joe Carey, Texas Biomed’s Vice President for Public Affairs, at 210-258-9437.

LOYOLA TESTING MELANOMA TREATMENT THAT BOOSTS PATIENT’S IMMUNE SYSTEM TO FIGHT DEADLY CANCER

Contact:

Jim Ritter
Media Relations
jritter@lumc.edu
(708) 216-2445
Anne Dillon
Director, Media Relations
adillon@lumc.edu
(708) 216-8232

 

MAYWOOD, Ill. – Loyola University Medical Center has launched the first clinical trial in the Midwest of an experimental melanoma treatment that genetically engineers a patient’s immune system to fight the deadly cancer.

 

 

A batch of the immune system’s killer T cells will be removed from the patient and genetically modified in a Loyola lab. Two genes will be inserted into the T cells so that they will recognize tumor cells as abnormal.

 

 

Patients will undergo high-dose chemotherapy to kill most of their remaining T cells. This will make room for the genetically modified T cells when they are put back in the patient. The modified T cells, it is hoped, will recognize the tumor cells as abnormal and then attack and kill them.

 

 

“This clinical trial is a unique attempt to manipulate a person’s own immune system to attack their cancer in a more effective and specific manner,” said Joseph Clark, MD, one of the principal investigators of the trial.

 

 

The purpose of the Phase 1 trial is to determine the optimum dose and whether the treatment is safe. Four doses will be tested, with the highest dose consisting of about 5 billion genetically modified T cells. If Phase 1 demonstrates the treatment is safe, investigators will proceed to Phase 2, which will determine whether the treatment is effective.

 

 

Melanoma is the sixth most common cancer in Americans, and the most common fatal malignancy in young adults. Incidence is rising dramatically. About 1 in 50 people will be diagnosed with melanoma. In the 1960s, it was 1 in 600.
Surgery is highly successful if the cancer is caught early. But if the cancer has spread to other parts of the body, the five-year survival rate is only 15 to 20 percent, according to the American Cancer Society.

 

 

“This is a terrible, devastating disease,” Clark said. “It starts on the skin and can spread to just about anywhere in the body.”

 

 

The clinical trial is open to patients with metastatic melanoma who are no longer responding to standard therapy. “We need better treatments,” Clark said. “Our clinical trial is designed for patients who have no other options.”

 

 

The experimental immune system therapy was developed by Michael I. Nishimura, PhD, director of the Immunotherapeutics Program at Loyola’s Cardinal Bernardin Cancer Center. The cells will be prepared in the Robert R. McCormick Foundation Center for Cellular Therapy in the Cardinal Bernardin Cancer Center.

 

 

Nishimura is principal investigator of a five-year, $16.3 million grant from the National Cancer Institute. “Our goal is to create novel therapies for the treatment of advanced malignancies,” he said.

 

 

Additional funding for the trial comes from a National Cancer Institute grant to Lentigen Corp., which makes the vector that delivers the genes to the T cells, and from the American Recovery and Reinvestment Act (the economic stimulus bill).

 

 

Clark is a professor in the Department of Medicine, Division of Hematology/Oncology of Loyola University Stritch School of Medicine. Nishimura is a professor in the Department of Surgery and associate director of the Oncology Institute of Loyola University Chicago Stritch School of Medicine.
Other investigators in the trial are Patrick Stiff, MD, director of the Cardinal Bernardin Cancer Center; Constantine Godellas, MD; Kelli Hutchens, MD; and Caroline Le Poole, PhD.

 

 

For more information, please call (708) 327-3221.