MSGID: 1:317/3 64a8e68a   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Fecal transplants show promise in improving melanoma treatment    
      
     Date:   
         July 7, 2023   
     Source:   
         Lawson Health Research Institute   
     Summary:   
         Researchers have found that fecal microbiota transplants (FMT)   
         from healthy donors are safe and show promise in improving response   
         to immunotherapy in patients with advanced melanoma.   
      
      
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   In a world-first clinical trial published in the journal Nature Medicine,   
   a multi-centre study from Lawson Health Research Institute, the Centre   
   hospitalier de l'Universite' de Montre'al (CHUM) and the Jewish General   
   Hospital (JGH) has found fecal microbiota transplants (FMT) from healthy   
   donors are safe and show promise in improving response to immunotherapy   
   in patients with advanced melanoma.   
      
   Immunotherapy drugs stimulate a person's immune system to attack and   
   destroy cancer. While they can significantly improve survival outcomes   
   in those with melanoma, they are only effective in 40 to 50 per cent of   
   patients. Preliminary research has suggested that the human microbiome   
   -- the diverse collection of microbes in our body -- may play a role in   
   whether or not a patient responds.   
      
   "In this study, we aimed to improve melanoma patients' response to   
   immunotherapy by improving the health of their microbiome through fecal   
   transplants," says Dr. John Lenehan, Medical Oncologist at London Health   
   Sciences Centre's (LHSC) London Regional Cancer Program (LRCP), Associate   
   Scientist at Lawson and Associate Professor in the Department of Oncology   
   at Western University's Schulich School of Medicine & Dentistry.   
      
   A fecal transplant involves collecting stool from a healthy donor,   
   screening and preparing it in a lab, and transplanting it to the   
   patient. The goal is to transplant the donor's microbiome so that healthy   
   bacteria will prosper in the patient's gut.   
      
   "The connection between the microbiome, the immune system and cancer   
   treatment is a growing field in science," explains Dr. Saman Maleki,   
   Scientist at Lawson and LHSC's LRCP, Assistant Professor in Schulich   
   Medicine's Departments of Oncology, Pathology and Laboratory Medicine,   
   and Medical Biophysics, and senior investigator on the study. "This study   
   aimed to harness microbes to improve outcomes for patients with melanoma."   
   The phase I trial included 20 melanoma patients recruited from LHSC, CHUM   
   and Jewish General Hospital. Patients were administered approximately   
   40 fecal transplant capsules orally during a single session, one week   
   before they started immunotherapy treatment.   
      
   The study found that combining fecal transplants with immunotherapy   
   is safe for patients -- which is the primary objective of a phase   
   I trial (also called 'safety trials'). The study also found 65 per   
   cent of patients who retained the donors' microbiome had a clinical   
   response to the combination treatment. Five patients experienced adverse   
   events sometimes associated with immunotherapy and had their treatment   
   discontinued.   
      
   "We have reached a plateau in treating melanoma with immunotherapy,   
   but the microbiome has the potential to be a paradigm shift," says   
   Dr. Bertrand Routy, Oncologist and Director of CHUM's Microbiome   
   Center. "This study puts Canada at the forefront of microbiome research   
   by showing we can safely improve patients' response to immunotherapy   
   through fecal transplants."  "These exciting results add to a rapidly   
   growing list of publications suggesting that targeting the microbiome   
   may provide a major advance in the use of immunotherapy for our patients   
   with cancer," adds Dr. Wilson H. Miller Jr.   
      
   of the JGH and Professor in the Departments of Medicine and Oncology at   
   McGill University.   
      
   The study is unique due to its administration of fecal transplants   
   (from healthy donors) in capsule form to cancer patients -- a technique   
   pioneered in London by Dr. Michael Silverman, Lawson Scientist, Chair   
   of Infectious Diseases at Schulich Medicine and Medical Director of the   
   Infectious Disease Care Program at St. Joseph's Health Care London.   
      
   "Our group has been doing fecal transplants for 20 years, initially   
   finding success treating C. difficile infections. This has enabled us to   
   refine our methods and provide an exceptionally high rate of the donor   
   microbes surviving in the recipient's gut with just a single dose," says   
   Dr. Silverman. "Our data suggests at least some of the success we are   
   seeing in melanoma patients is related to the efficacy of the capsules."   
   The team has already started a larger phase II trial involving centres in   
   Ontario and Quebec. Lawson researchers are also studying the potential   
   of fecal transplants in the treatment of other cancers, including renal   
   cell carcinoma, pancreatic cancer and lung cancer, as well as HIV and   
   rheumatoid arthritis.   
      
   This research is supported in part through donor funding from London   
   Health Sciences Foundation, Western University, the Lotte and John Hecht   
   Memorial Foundation, the JGH Foundation, Canadian Cancer Society's Impact   
   Grant program and The Terry Fox Foundation.   
      
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   Journal Reference:   
      1. Bertrand Routy, John G. Lenehan, Wilson H. Miller, Rahima Jamal,   
      Meriem   
         Messaoudene, Brendan A. Daisley, Cecilia Hes, Kait F. Al, Laura   
         Martinez- Gili, Michal Punčocha'ř, Scott Ernst, Diane   
         Logan, Karl Belanger, Khashayar Esfahani, Corentin Richard,   
         Marina Ninkov, Gianmarco Piccinno, Federica Armanini, Federica   
         Pinto, Mithunah Krishnamoorthy, Rene Figueredo, Pamela Thebault,   
         Panteleimon Takis, Jamie Magrill, LeeAnn Ramsay, Lisa Derosa,   
         Julian R. Marchesi, Seema Nair Parvathy, Arielle Elkrief, Ian   
         R. Watson, Rejean Lapointe, Nicola Segata, S.M. Mansour Haeryfar,   
         Benjamin H. Mullish, Michael S. Silverman, Jeremy P. Burton, Saman   
         Maleki Vareki. Fecal microbiota transplantation plus anti-PD-   
         1 immunotherapy in advanced melanoma: a phase I trial. Nature   
         Medicine, 2023; DOI: 10.1038/s41591-023-02453-x   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/07/230707111654.htm   
      
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