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

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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479091/
https://www.ncbi.nlm.nih.gov/pubmed/34584159
http://dx.doi.org/10.1038/s41598-021-98716-z
Descripción
Sumario: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.