22 Nov Sanofi Studies Trispecific Antibody to Improve Cancer Immunotherapy

MedicalResearch.com Interview with:

Dr. Nabel

Dr. Gary J. Nabel M.D., Ph.D.
Chief Scientific Officer, Global Research and Development
Sanofi

MedicalResearch.com: What is the background for this study?

Response: The power of T cell co-stimulation in the immune system became apparent to the immunology community from basic studies on T cell activation and T cell receptor function dating back to the 1980’s and 1990’s.  As a professor at the University of Michigan and investigator at its Howard Hughes Medical Institute in the 1990’s, I became aware of this pathway through collaborations with Carl June and Craig Thompson in the 1990s.  When we stimulated T cells by engaging CD3 (a T cell receptor activation signal e.g. signal 1) and CD28 (a survival signal e.g. signal 2), we found that the co-stimulatory effect led to exceptional T cell proliferation.

After our Sanofi team developed the trispecific antibody technology, we realized that it might be possible to engage CD3 and CD28 while targeting T cells to tumors with a third arm, CD38, which is highly expressed on myelomas, all interactions mediated by this one protein. 

MedicalResearch.com: What are the main findings?

Response: Our findings published online on 18 November in the first issue of Nature Cancer were performed by a Sanofi research team that evaluated a novel trispecific antibody against human myelomas in cell culture and in animals. It represents an attempt to improve the efficacy of cancer immunotherapy by targeting multiple sites on tumors and lymphocytes in order to stimulate, strengthen and direct the body’s natural defenses against a cancer.

MedicalResearch.com: What should readers take away from your report?

Response: Multispecific therapeutic antibodies have potential to improve immunotherapy of cancer. We know that the many cancers escape immune recognition that could otherwise eliminate them. Here we have demonstrated the value of T cell co-stimulation to optimize T cell activation and recognition of cancer cells. The trick is to use the multi-functionality of the trispecific antibody to target tumors, in this case through CD38, while delivering signals that recruit and stimulate T cells to lyse the tumor in order to more effectively eliminate them.

While, we still have much work to do to determine whether this multi-specific targeted approach stimulates tumor regression in people with cancer, this outcome is encouraging and is opening research avenues to help us achieve our goal to bring new immuno-therapies that help to harness the full potential of our body’s immune system to defeat cancer.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: The next step is to progress this novel trispecific antibody to clinical trials in order to fully evaluate its safety and efficacy against cancer in humans. At Sanofi, we are particularly focused on safety and tolerability that will be assessed in phase 1 studies, with special attention to immune/inflammatory side effects as doses are escalated.  We will also be looking at proof of concept for this therapy by measuring tumor growth and anti-tumor immunity.

MedicalResearch.com: Is there anything else you would like to add?

Response: This approach is potentially applicable to several types of cancer and requires close collaborations with experts in cancer immunotherapy. For this reason, Sanofi is committed to collaborating with renowned cancer research organizations worldwide in order to inform the design and target population for our clinical studies. The goal is to identify robust biomarkers that will help us match the right therapeutic approach with the right patient population to optimize clinical outcomes with new and existing therapies alone and in combination.

Citation:

Wu, L., Seung, E., Xu, L. et al. Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation. Nat Cancer (2019) doi:10.1038/s43018-019-0004-z

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Last Updated on November 27, 2019 by Marie Benz MD FAAD