Summary: Cancer neoantigens are highly specific to the tumor, potently immunogenic and can be targeted by both vaccines and engineered cellular therapies. This talk will introduce the definition of cancer neoantigens, review the neoantigen source, and discuss the challenges of neoantigen discovery from tumor genomic sequencing data. In addition, I will talk about a phase-I clinical trial design for neoantigen vaccine therapy at Mayo Clinic.
Background: Immune Checkpoint Inhibitors (ICI) and Chimeric Antigen Receptor T-cells (CAR-T) are the two major immunotherapies that have revolutionized cancer treatments. Despite the immense promise of immunotherapies in treating various cancers, there have been a wide range of responses from patients. The percent of US patients with cancer who are eligible for ICI drugs increased to 43.63% in 2018 however only 12.46% of these patients are estimated to respond to ICI treatments. CAR-T has reached revolutionary milestone in treatment of hematological malignancies. However, CAR-T has not been yet successful in treating solid cancers due to the limited repertoire of cell-surface antigens and its ineffectiveness of infiltrating into solid tumor tissues. Furthermore, CAR-T therapy is not tumor-specific. The surface proteins targeted by CAR-T to-date are also expressed on normal cells resulting in on-target off-tumor and even off-target toxicities. In addition, significant challenges have been mounting to overcome treatment resistance and to improve efficacy. Strategies such as the combination immunotherapies of existing agents have so far yielded more failures than successes in this effort. Therefore, we have reached a critical point where it’s essential to search for and develop the novel next generation immunotherapy agents. Cancer neoantigens are among the most promising novel agents.
1. Discuss the different types of tumor somatic mutations that are sources of neoantigens.
2. Break down the bioinformatics approaches for neoantigen identification from genomic sequencing data.
3. Discuss basic design for phase-I neoantigen clinical trials.