The remarkable results of clinical studies on immune checkpoint inhibitors have opened a new window into cancer immunotherapy. Instead of “enhancing the activation” of antitumor immunity, “blocking the suppression” of cancer cells has brought a paradigm shift in cancer immunotherapy.
These immune checkpoint inhibitors are currently effective in only 10–30% of cancer patients. There are more than 800 ongoing clinical trials for immune checkpoint inhibitors and combination therapies. In addition, next generation sequencing allows for full characterization of genetic alterations and transcript abundance in individual tumors. Researchers in cancer immunology are further developing in vitro and in vivo immune monitoring and profiling technologies. The application of therapeutics coupled with powerful bioinformatic and immunological techniques will promote the understanding of how and why a patient responds to therapy in more detail.
Vaccines and checkpoint antibodies are notably crucial combination in the cancer immunotherapies. When the naive immune response to cancer is weak, a vaccine will be effective. When a tumor shields themself from the immune system, a checkpoint inhibitor can unshield it, making the tumor visible to the immune system (in combination with cancer vaccines). When a tumor generates a hostile microenvironment that suppresses the local immune response against the tumor, the tumor microenvironment is a potential target for synergism with cancer immunotherapy (in combination with immunomodulators). As cancer immunotherapy is a part of the major trend of personalized medicine, ongoing research includes identifying biomarkers for efficacy prediction, increasing therapy options for the patient through different combinations, and modifying therapies to make them effective in patients who do not respond to their current therapy. Based on the current state of cancer immunotherapy, we are developing technologies that straddle different areas and modalities of cancer immunotherapy.
Furthermore, two recent state-of-the-art technologies, high-throughput next generation sequencing and bioinformatics, allow for fully personalized cancer vaccination. The use of “neoantigens” is a new approach to cancer vaccines, which carry the exact mutations found in the patient’s tumor. These neoantigens are genetically non-self; thus, they appear as foreign to the immune system, and are capable of inducing a strong immune response. The results of recent clinical trials of checkpoint inhibitors have suggested that the immune rejection of tumors observed after administration of checkpoint inhibitors is mediated by the recognition of neoantigens.
We are developing multiple therapeutic vaccines and T cell modalities targeting cancer antigens shared across patients as well as neoantigens specific to individual patients. By taking a multimodality approach with a broad portfolio, we hope to integrate with complementary immunotherapies to significantly improve patient response to treatment. We also believe that our work will help us to bring the right therapy to each cancer patient, as well as provide scientific insights into cancer immunology.