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SITC 2022: Antigen-Specific Memory CD8-Positive T Cells Target BCMA to Treat Multiple Myeloma

By: Gavin Calabretta, BS
Posted: Tuesday, November 15, 2022

A group of researchers from Dana-Farber Cancer Institute, Boston, recently developed a protocol for the ex vivo isolation and expansion of B-cell maturation antigen (BCMA)-specific memory CD8-positive T lymphocytes. According to Jooeun Bae, PhD, and colleagues, the protocol builds on an existing vaccination strategy that previously induced antigen-specific memory T cells against targets including X-box binding protein 1, Syndecan-1, and SLAMF7, which are highly expressed in multiple myeloma cells. These findings were presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 812).  

“These results provide the framework for combining BCMA-peptide vaccination and the specific cellular therapy using the vaccine-induced [interferon gamma-positive] memory T cells to further enhance [anti–multiple myeloma] immunity,” the study authors remarked.

After first adapting the vaccination strategy to target BCMA, the investigators developed the expansion protocol, which is designed to follow the induction of multiple myeloma–specific CD8-positive T lymphocytes. The team reported that the resulting CD8-positive T lymphocytes showed upregulation of several costimulatory molecules, including CD28, 4-1BB, CD40L, and OX40. Among several evaluated conditions, anti-CD3 and CD28 stimulation resulted in the greatest expansion of BCMA-specific CD8-positive T lymphocytes over a 2-week period and specifically induced the proliferation of antigen-specific central memory CD8-positive T lymphocytes (47% with anti-CD3 and CD28 treatment vs. 6% without).

Attempting to increase the efficacy of the cell product, the study authors sorted and expanded functionally active BCMA-specific interferon gamma-positive CD8-positive T lymphocytes with anti-CD3 and CD28, interleukin (IL)-2, and IL-15. A significant, continuous expansion of BCMA-specific CD8-positive T lymphocytes was achieved under these conditions, and high IL-2 and TNF-alpha cytokine production alongside antitumor activity was also observed.

Disclosure: No disclosure information was provided.

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