Tenzin Yangdon

Program: Immunology

Current advisor: Nathan Singh, MD, MS

Undergraduate university: Macalester College, 2019

Enrollment year: 2022

Research summary
A high relapse rate remains an issue in CAR T therapy, with patients developing antigen-negative cancer cells, rendering CART therapy ineffective. Here, we propose a novel approach that combines CAR T cell therapy with neo-peptide vaccine therapy.

CAR T cell therapy involves genetically engineering a patient’s T cells to express a chimeric receptor that recognizes specific tumor antigens, enabling the T cells to target and kill the tumor cells. Currently, six CAR T therapies have been approved by the FDA for the treatment of hematological malignancies, with a remission rate of around 70%. However, despite these promising results, a high relapse rate remains an issue, with many patients experiencing the development of antigen-negative cancer cells, which renders CAR T therapy ineffective. Additionally, CAR T therapies have shown limited efficacy in solid tumors, primarily due to the physical barriers imposed by the tumor extracellular matrix and the immunosuppressive tumor microenvironment, which hinder CAR T cells’ ability to effectively kill cancer cells. To address this limitation, we propose a novel approach that combines CAR T cell therapy with neo-peptide vaccine therapy. In this approach, we have engineered CAR T cells to secrete tumor-specific neopeptides directly within the tumor microenvironment to engage more tumor-specific endogenous T cells. Clinical trials targeting neopeptides have shown encouraging results in cancers such as non-small cell lung carcinoma, pancreatic cancer, and synovial sarcoma, with evidence suggesting that neopeptide-based vaccines can help prevent disease progression and recurrence. Therefore, we predict that combining CAR T with neopeptide therapy will provide an enhanced and specific killing of tumor cells. This dual action enhances overall tumor killing and helps overcome the growth of CAR T antigen-negative cancer cells, a common challenge in patients undergoing CAR T therapy.

Graduate publications