A multiantigen-targeting cytotoxic CD4+ T cell approach for treating B cell malignancies
Baochun Zhang
PhD, MDDana-Farber Cancer Institute
Project Term: July 1, 2019 - June 30, 2022
B cell malignancies comprise a large number of different types of lymphomas and leukemia, which collectively represent the sixth leading cause of cancer death in the US. These cancer cells are potential targets of the host immune system’s CD4+ T cells, however, the latter normally lack the ability to kill such cancer cells. In this project, we develop a novel approach to rapidly produce CD4+ T cells capable of killing B cell cancers, and advance this approach towards clinical trials.
B cell malignancies – cancers arising from blood B cells – comprise a large number of different types of lymphomas and leukemia, which collectively represent the sixth leading cause of cancer death in the US. New treatments, particularly various immunotherapy approaches, are under active development and testing. These immunotherapy approaches predominantly utilize immune system’s CD8+ T cells to identify and kill cancer cells, but they produce durable remissions only in a fraction of B cell cancer patients. Thus, alternative immune approaches need to be developed. Cancerous B cells are potential targets of the immune system’s CD4+ T cells, yet, the latter normally lack the ability to kill such cancer cells. In this project, we develop a novel approach to rapidly produce CD4+ T cells capable of killing cancerous B cells; we will test and optimize the produced CD4+ T cells for treating B cell malignancies in preclinical animal models, and prepare this approach towards clinical trials in patients with chronic or acute B cell leukemia. Once proven effective, this CD4+ killer T cell-based immunotherapy could easily be extended to any other B cell malignancy.