Researchers from John Hopkins have invented a new drug that can boost the immune system to fight cancer. The work was published in Nature Communications.
"The immune system is naturally able to detect and eliminate tumor cells. However, virtually all cancers—including the most common cancers, from lung, breast and colon cancers to melanomas and lymphomas—evolve to counteract and defeat such immune surveillance by co-opting and amplifying natural mechanisms of immune suppression," says Atul Bedi, senior author of the study.
One of the ways tumors take advantage of the immune system is by promoting regulatory
T cells (Tregs), which suppress immune responses. "This is especially challenging because Tregs are not only induced by the TGFβ (transforming growth factor-beta), a protein made by tumor cells, but make their own TGFβ to maintain their identity and function in the tumor," says Bedi. In addition, Tregs also produce cytotoxic T-lymphocyte associated protein 4 (CTLA-4), which prevents anti-tumor immune cells from acting.
So the team invented Y-traps, which are immunotherapy drugs that they designed to target CTLA-4 and trap TGFβ. To test their new creation, they transplanted human cancer cells into mice engineered to have human immune cells. They found that their traps worked and eliminated Treg cells in tumors and slowed tumor growth that failed to respond to ipilimumab, a current immunotherapy drug that targets the CTLA-4 protein.
Another target that many cancer immunotherapies go after is protein, PD-1, or its ligand (PD-L1). So the team designed a Y-trap targeting PD-L1 and trapping TGFβ. Again, they found that their Y-trap worked and actually even better than other drugs that target PD-1 or PD-L1.
"These first-in-class Y-traps are just the beginning. We have already invented a whole family of these multifunctional molecules based on the Y-trap technology. Since mechanisms of immune dysfunction are shared across many types of cancer, this approach could have broad impact for improving cancer immunotherapy," says Bedi. "Y-traps could also provide a therapeutic strategy against tumors that resist current immune checkpoint inhibitors."