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01.02.2013 | Original article

MHC-class I-restricted CD4 T cells: a nanomolar affinity TCR has improved anti-tumor efficacy in vivo compared to the micromolar wild-type TCR

verfasst von: Carolina M. Soto, Jennifer D. Stone, Adam S. Chervin, Boris Engels, Hans Schreiber, Edward J. Roy, David M. Kranz

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 2/2013

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Abstract

Clinical studies with immunotherapies for cancer, including adoptive cell transfers of T cells, have shown promising results. It is now widely believed that recruitment of CD4⁺ helper T cells to the tumor would be favorable, as CD4⁺ cells play a pivotal role in cytokine secretion as well as promoting the survival, proliferation, and effector functions of tumor-specific CD8⁺ cytotoxic T lymphocytes. Genetically engineered high-affinity T-cell receptors (TCRs) can be introduced into CD4⁺ helper T cells to redirect them to recognize MHC-class I-restricted antigens, but it is not clear what affinity of the TCR will be optimal in this approach. Here, we show that CD4⁺ T cells expressing a high-affinity TCR (nanomolar K _d value) against a class I tumor antigen mediated more effective tumor treatment than the wild-type affinity TCR (micromolar K _d value). High-affinity TCRs in CD4⁺ cells resulted in enhanced survival and long-term persistence of effector memory T cells in a melanoma tumor model. The results suggest that TCRs with nanomolar affinity could be advantageous for tumor targeting when expressed in CD4⁺ T cells.

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Titel: MHC-class I-restricted CD4 T cells: a nanomolar affinity TCR has improved anti-tumor efficacy in vivo compared to the micromolar wild-type TCR
verfasst von: Carolina M. Soto
Jennifer D. Stone
Adam S. Chervin
Boris Engels
Hans Schreiber
Edward J. Roy
David M. Kranz
Publikationsdatum: 01.02.2013
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 2/2013
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-012-1336-z

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Springer Medizin

MHC-class I-restricted CD4 T cells: a nanomolar affinity TCR has improved anti-tumor efficacy in vivo compared to the micromolar wild-type TCR

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

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