Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells

基于肽-HLA的免疫治疗平台,用于直接调节抗原特异性T细胞

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作者:Ronald D Seidel, Zohra Merazga, Dharma Raj Thapa, Jonathan Soriano, Emily Spaulding, Ahmet S Vakkasoglu, Paige Ruthardt, Wynona Bautista, Steven N Quayle, Peter A Kiener, Simon Low, John F Ross, Saso Cemerski, Anish Suri, Steven C Almo, Rodolfo J Chaparro

Abstract

Targeted pharmacologic activation of antigen-specific (AgS) T cells may bypass limitations inherent in current T cell-based cancer therapies. We describe two immunotherapeutics platforms for selective delivery of costimulatory ligands and peptide-HLA (pHLA) to AgS T cells. We engineered and deployed on these platforms an affinity-attenuated variant of interleukin-2, which selectively expands oligoclonal and polyfunctional AgS T cells in vitro and synergizes with CD80 signals for superior proliferation versus peptide stimulation.

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