Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells
R.D. Seidel, Zohra Merazga, Dharma R. Thapa, Jonathan Soriano, Emily Spaulding, Ahmet S. Vakkasoglu, Paige Ruthardt, Wynona Bautista, Steven N. Quayle, Peter A. Kiener, Simon Low, John F. Ross, Sašo Čemerski, Anish Suri, Steven C. Almo, Rodolfo 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.