Drew Weissman, MD, PhD

Developing and testing a novel vaccine for triple-negative breast cancer.

Impact

Triple-negative breast cancer (TNBC) is the most aggressive and deadly form of the disease with only 35 to 45 percent of patients responding to standard-of-care chemotherapy with complete tumor clearance. TNBC has a high propensity to spread to other organs and tissues, and the 5-year survival rate for metastatic disease is only 11 percent. Thus, there is an urgent need to develop new treatments for TNBC. These tumors have a high degree of gene mutations which lead to the production of tumor-specific proteins called tumor-associated antigens (TAAs). Dr. Weissman and his team are exploiting these findings to develop a novel TNBC vaccine to advance personalized care and expand the use of immunotherapy against TNBC that currently has few options.

Progress Thus Far

Dr. Weissman and his colleagues are leveraging cutting-edge lipid nanoparticle (LNP) technology to construct mRNA-LNP vaccines against TNBC. The lipids serve to encapsulate the otherwise fragile mRNA and allow it to pass through the immune cell membrane. There, the antigen-encoding mRNA produces the specific antigen to stimulate the body’s immune system. Dr. Weissman and his colleagues have developed laboratory models that reproduce the molecular features of TNBC cells. Further, the models were engineered to express specific antigens that can be recognized by the mRNA-LNP based cancer vaccines they have designed. In addition to developing a model system for vaccine testing, they also looked at ways to help make mRNA-LNP based cancer vaccines more effective. Since cytokines are proteins involved in immune signaling and some of them have been shown to help fight tumors, his team tested two cytokines, IL12 and IL27, as potential adjuvants for vaccination. They showed both cytokines to increase the magnitude of the immune response, suggesting their inclusion in future vaccine formulations could be highly promising.

What’s next

Dr. Weissman and his team will continue to develop and test mRNA-LNP vaccines in laboratory studies. Based on preliminary data, they will adjust the mRNA-LNP formulations to obtain the most effective version. Building on their results, they will also develop more sophisticated laboratory models for rigorous testing of the vaccine with the goal to translate their findings to the clinic.