Bispecific Antibody Recruitment to Increase Antitumor Activity of Adoptive T-Cell Transfer

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In a study reported in the Journal of the National Cancer Institute, Kobold and colleagues assessed whether combining tumor-specific T cells modified with a marker antigen and a bispecific antibody that selectively recognizes transduced T cells and tumor cells could improve T-cell recruitment to tumors and antitumor activity of adoptive T-cell transfer.

SV40 T antigen–specific T cells from T-cell receptor-I transgenic mice were transduced with truncated human epidermal growth factor receptor (EGFRa) as a marker protein. Targeting and killing with combined adoptive T-cell therapy and anti-EGFR/anti-epithelial cell adhesion molecule bispecific antibody therapy were investigated in C57BL/6 mice with murine gastric cancer cell line GC8 (positive for both SV40 and epithelial cell adhesion) subcutaneous tumors. Anti-EGFR/anti-c-Met bispecific antibody was used for targeting of human tumor-specific T cells to c-Met–positive human tumor cell lines. The bispecific antibody linked EGFR-transduced T cells to tumor cells and increased tumor cell lysis.

In mouse models, the combination of adoptive T-cell transfer and bispecific antibody increased T-cell infiltration of tumors, inhibited tumor growth, and prolonged survival compared with adoptive T-cell transfer with a control antibody (median survival 95 vs 75 days, P < .001).

In human cells, the bispecific antibody strategy increased recruitment of human EGFR-transduced T cells to immobilized c-Met and improved recognition of tyrosinase-positive melanoma cells by T-cell receptor–modified T cells and carcinoembryonic antigen–positive colon cancer cells by chimeric antigen receptor–modified T cells.

The investigators concluded: “Bispecific antibody recruitment of tumor-specific T cells transduced with a marker antigen to tumor cells may enhance efficacy of [adoptive T-cell transfer].” ■

Kobold S, et al: J Natl Cancer Inst 107:364, 2014 (print January 2015).




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