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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Friday, November 15, 2024
Novel work has provided the first proof of concept in murine models that ex vivo–engineered B cells, specific for a tumor-associated antigen, may expand an assemblage of anticancer B cells. Lucia Sereni, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues presented their research at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 1140). The investigators believe their results may lead to new strategies for combining active and passive cancer immunotherapies in breast and other cancers.
Antigen-specific B cells appreciably affect cancer prognosis, said the authors. In patients with HER2-positive breast cancer, HER2-specific B cells have been correlated with reduced recurrence and improved chemotherapy response, the investigators noted.
Preclinical research had suggested that transferring tumor-specific B cells may inhibit tumor progression and boost T-cell immunity. So, the team set out to use a CRISPR-based B-cell receptor–editing strategy to insert a clinical anti-HER2 antibody into the endogenous heavy chain locus of mouse and human B cells.
The edited B cells successfully expressed the HER2 B-cell receptor, responded to B-cell receptor–mediated signaling, and secreted the engineered antibody, according to Dr. Sereni and co-investigators. Further, in the murine breast cancer model, a chemotherapy regimen prior to transplant “increased homing to the tumor; boosted germinal center reactions of host B cells in the tumor-draining lymph node, inguinal lymph node, and spleen; and slowed down tumor growth,” they wrote. “Similarly, the adoptive transplant of edited human B cells into peripheral blood mononuclear cell–humanized NSG mice resulted in significant tumor reduction, increased tumor infiltration by transplanted B cells and by CD4 T cells, and production of anti-HER2 antibodies.”
Of note, they found that tumor reduction directly correlated with T-cell expansion—but not with antibody levels. After in vitro rechallenge with tumor cells, they saw an increase in interferon gamma–producing T cells, suggesting, they said, a boost in tumor-reactive T cells.
Disclosure: No disclosure information was provided.
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