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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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:
Article
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
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author 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.
author_facet 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.
author_sort Seidel, Ronald D.
collection PubMed
description 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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spelling pubmed-84790912021-09-30 Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells 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. Sci Rep Article 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. Nature Publishing Group UK 2021-09-28 /pmc/articles/PMC8479091/ /pubmed/34584159 http://dx.doi.org/10.1038/s41598-021-98716-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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.
Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells
title Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells
title_full Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells
title_fullStr Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells
title_full_unstemmed Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells
title_short Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells
title_sort peptide-hla-based immunotherapeutics platforms for direct modulation of antigen-specific t cells
topic Article
url 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
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