TCR Gene-modified Peripheral Blood T cells Against Metastatic Melanoma

Rohaan MW, Gomez-Eerland R, van den Berg JH, et al. MART-1 TCR Gene-Modified Peripheral Blood T Cells for the Treatment of Metastatic Melanoma: A Phase I/IIa Clinical Trial. IOTECH. 2022; 15 (doi: 10.1016/j.iotech.2022.100089).

Researchers describe their development of a good manufacturing practice process for generating and transferring T-cell receptor (TCR) gene-modified peripheral blood T cells to be used as immunotherapy for metastatic melanoma. The adoptive cell therapy (ACT), known as 1D3HMCys, involves the transfer to autologous T cells expressing melanoma antigen recognized by T cells 1 (MART-1). The TCR-engineered cells are expanded in the presence of interleukin (IL)-7 and IL-15 and are cultured to have less differentiated phenotypes. The end product is highly reactive T cells. In a Phase I/IIa clinical study, 12 melanoma patients each received a single infusion of transgenic T cells in a dose-escalating manner. Transfused cells persisted for up to 9 months and correlated to cell dose, which was tolerated at no higher than 1.0 x 108 gene-modified T cells. Antitumor activity was modest, with 18% of the 11 patients exhibiting partial response at tolerable levels but toxicity growing more severe at higher doses. Although the toxic effects brought the trial to an early stop, investigators believe the research may represent a viable strategy for improving ACT.

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Tags: patient care, transplantation, Peripheral, immunotherapy, response, Metastatic, Melanoma, T-Cell, toxicities, antigen, Autologous, t-cell therapy, peripheral blood, gene