Our Research Has Supported Dr. Jedd Wolchok and his lab who have been at the forefront of melanoma research, changing the way we treat cancer.
Defining the Best Treatment Options for Metastatic Melanoma
Our group has pioneered the use of immunotherapy for metastatic melanoma, and this has resulted in a great than 10-fold improvement in 5 year survival statistics. Long-term follow-up from the CheckMate-067 global clinical trial, designed and led by our group, has recently been published in the Journal of Clinical Oncology. A separate trial, which we contributed to, defined immunotherapy as the best choice of first treatment. This was also recently published in the Journal of Clinical Oncology.
Advancing Chemoimmunotherapies Mechanistically
In a recent study, the lab showed that a combination of immunotherapy and chemotherapy was successful in mobilizing certain T cells to fight tumors. T cells play an important role in protecting the body against harmful diseases, but they can also be responsible for turning the immune system off when it should be on. By targeting GITR, a protein that helps regulate the activity of T cells, our team found a promising way to trigger an immune response in patients who have been historically unresponsive to immunotherapy. “Cyclophosphamide Enhances the Anti-Tumor Potency of GITR Engagement by Increasing Oligoclonal Cytotoxic T Cell Fitness” was published in JCI Insight in October 2021.
Modeling Mutational Hot Spots
Another study from our lab considered why certain gene areas are more likely to mutate in established tumors than others, a question that has long puzzled oncologists. By collaborating with physicists and mathematicians modeling the emergence of mutational hot spots in TP53, the most mutated gene in cancer, we were able to study an important interplay between gene mutations and their ability to activate the immune system. These data were published in “Fundamental Immune–Oncogenicity Trade-offs Define Driver Mutation Fitness” in Nature in May 2022.
(re-)Discovering T Cell Subtypes
Our lab has also made important progress in understanding the different types of T cells. Classical teaching stresses that double-positive T cells, which express both the CD4 and CD8 proteins are vastly reduced in number during fetal development as single positive cells dominate. We recently found that tumors can induce the expression of double-positivity in tumor reactive T cells. This is important because some of these double positive cells are uniquely equipped to kill cancer cells. This knowledge is immediately usable in designing new therapeutic strategies. We also learned that the fate of T cells is not ‘written in stone’ and that a given T cell may change not only the way it looks in terms of molecular markers, but also may adopt new functional skills. The study, “Tumor-Induced Double Positive T Cells Display Distinct Lineage Commitment Mechanisms and Functions,” was published in the Journal of Experimental Medicine in May 2022.
Live4Life Continues To Make a Difference in Patients With Advanced Melanoma
This is an extremely exciting time for cancer research. Our understanding of molecular biology in cancer is increasing rapidly, and that is leading to new therapeutic strategies and new agents. Live4Life and MSK significantly improve the lives of cancer patients.
Medical oncologist Jedd D. Wolchok, MD, PhD, is one of the leaders in this field. His work is dedicated to the development of novel ways to use the immune system to fight melanoma. Just this year, the U.S. FDA approved two new drugs to treat metastatic melanoma: Ipilimumab (Yervoy) takes the breaks off the immune system to allow the immune system to become more activated than it otherwise would, resulting in the creation of antibodies and T cells that can recognize melanoma and control the disease. It is the first drug ever to show an improvement in survival in patients with metastatic melanoma. Before ipilimumab, there were only two drugs approved in the U.S. to treat melanoma, and there has not been a new drug approved in over 13 years. B-RAF inhibitor (Vemurafenib) causes programmed cell death in melanoma cell lines. It works in patients who have the B-RAF mutation, which is approximately 60% of patients.
The Live4Life Foundation has been our partner from the beginning and has been instrumental in supporting these developments. This is a momentous time for our patients and for MSK’s physician-scientists. This important work could not have been achieved without the generosity of the Live4Life Foundation.
The next steps in this work include learning how to combine these drugs with other important medicines to treat cancer. Through these drugs, we have extended survival for 20% to 30% of people with advanced melanoma, but this is not good enough. We want to make a difference in 100% of melanoma patients. Dr. Wolchok is now engaged in a study examining the combination of ipilimumab and anti-PD1 antibodies for the treatment of metastatic melanoma. The purpose of the study is to understand how these two therapies may interact when combined. This phase 1 study is now open only at MSKCC and Yale and presents a unique opportunity to learn in real-time about what factors define successful melanoma treatment from the standpoint of the immune system.
Please continue to support Live4Life Foundation’s efforts. They really do make a difference in the lives of patients with advanced melanoma. Without your support, physicians like Dr. Wolchok would not have the funds to make collaborations, interact with scientists and statisticians, develop clinical trials, and analyze data.
Click on the links below to read about advances in Melanoma treatment:
Novel Immunotherapy Drug Receives FDA Approval for the Treatment of Metastatic Melanoma
Melanoma Treatment Harnesses Immune System To Combat Cancer Cells
Click here for the latest articles about Dr. Wolchok and the news at ASCO.
https://www.wsj.com/articles/SB10001424127887323398204578485401089823868