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

• Published in: Scientific reports Vol. 11; no. 1; p. 19220
• Main Authors: Seidel, Ronald D., Merazga, Zohra, Thapa, Dharma Raj, Soriano, Jonathan, Spaulding, Emily, Vakkasoglu, Ahmet S., Ruthardt, Paige, Bautista, Wynona, Quayle, Steven N., Kiener, Peter A., Low, Simon, Ross, John F., Cemerski, Saso, Suri, Anish, Almo, Steven C., Chaparro, Rodolfo J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.09.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/61; Animals; Antigens; B7-1 Antigen - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD80 antigen; Cell activation; Cell proliferation; Cells, Cultured; Histocompatibility antigen HLA; HLA-A Antigens - genetics; HLA-A Antigens - immunology; Humanities and Social Sciences; Humans; Immunotherapy; Immunotherapy - methods; Interleukin 2; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Mice; Mice, Transgenic; multidisciplinary; Mutation; Neoplasms - immunology; Neoplasms - therapy; Peptides; Peptides - genetics; Peptides - immunology; Primary Cell Culture; Protein Engineering; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-98716-z

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.