Advancements in the fight against cancer are steadily pushing the boundaries of medicine, as a team of MIT researchers have reportedly designed a therapeutic cancer vaccine with promising potential. As part of their research, which was recently published in the Journal for Immunotherapy of Cancer, they explored ways to enhance the effectiveness of immune checkpoint blockade (ICB) therapies, which aid the immune system in identifying and attacking cancer cells. The study was led by Stefani Spranger, associate professor of biology at MIT, and included contributions from Forest White and Darrell Irvine, experts in their respective fields.
ICB therapies work by interfering with the proteins cancer cells use to evade the immune system. While effective in some instances, their efficacy varies due to the complex nature of tumor antigen distribution. Tumors with a homogeneous antigen presence tend to respond better to treatments than those that are heterogenous—where varied antigens across cell populations present a challenge. In an effort to improve responses in heterogenous tumors, which represents the overwhelming majority of tumors, the research team at MIT set their sights on understanding the intricate antigen patterns that enable cancer to circumvent immune detection.
Utilizing mouse models of lung cancer, both "clonal" and "subclonal" tumors were studied to determine the influence of different antigen patterns on the immune system's T cells. They discovered that it’s not merely the presence of antigens that matters, but also the scope of their expression across a tumor, the interplay of co-expressed antigens, and each antigen’s binding characteristics. According to Spranger, “It’s not so black-and-white,” stressing the importance of moving beyond numerical analysis to explore the dynamics between antigen hierarchies. This insight underscores the potential for new and improved therapeutic strategies, as per MIT News.
Surprisingly, their findings showed that in the case of subclonal tumors, treatments that initially kept strong-antigen-expressing cells under control could later fail as other tumor segments without the strong antigen grew resistant to ICB therapy. To tackle this, the researchers designed an RNA-based vaccine to complement ICB treatment—leading to control over tumors in their mouse models, regardless of the antigens' binding affinities. The vaccine’s efficacy hinged on the uniform expression of the targeted antigen across the tumor cells.
An analysis of clinical data also suggested that the combination of vaccine and ICB therapy holds potential for patients with tumors exhibiting high heterogeneity. The team's ongoing work, in collaboration with the Irvine laboratory at Scripps Research Institute, aims to refine the vaccine for eventual clinical testing. Stefani Spranger expressed the value of overlooked antigen targets, telling MIT News, "Even antigens that don’t make the numerical cut-off could be really valuable targets." With this innovative approach, there's growing optimism for more effective cancer treatments on the horizon.
