PD1-CD28 Fusion Protein Enables CD4+ T Cell Help for Adoptive T Cell Therapy in Models of Pancreatic Cancer and Non-hodgkin Lymphoma

Frontiers in Immunology
Felicitas RatajSebastian Kobold

Abstract

Background: Interaction of the programmed death receptor 1 (PD-1) and its ligand, PD-L1, suppresses T cell activity and permits tumors to evade T cell-mediated immune surveillance. We have recently demonstrated that antigen-specific CD8+ T cells transduced with a PD1-CD28 fusion protein are protected from PD-1-mediated inhibition. We have now investigated the potential of PD1-CD28 fusion protein-transduced CD4+ T cells alone or in combination with CD8+ T cells for immunotherapy of pancreatic cancer and non-Hodgkin lymphoma. Methods: OVA-specific CD4+ and CD8+ were retrovirally transduced with the PD1-CD28 fusion protein. Cytokine release, proliferation, cytotoxic activity, and phenotype of transduced T cells were assessed in the context of Panc02-OVA (murine pancreatic cancer model) and E.G7-PD-L1 (murine T cell lymphoma model) cells. Results: Stimulation of PD1-CD28 fusion protein-transduced CD4+ T cells with anti-CD3 and recombinant PD-L1 induced specific T cell activation, as measured by IFN-y release and T cell proliferation. Coculture with Panc02-OVA or E.G7-PD-L1 tumor cells also led to specific activation of CD4+ T cells. Cytokine release and T cell proliferation was most effective when tumor cells simultaneously encount...Continue Reading

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Citations

Sep 24, 2020·Immunological Reviews·Chirine RafiaEmmanuel Scotet
May 22, 2019·Cells·Stefan StoiberSebastian Kobold
Jul 28, 2020·Cells·Francesca SillitoHans J Stauss
Nov 27, 2018·Experimental Hematology & Oncology·Ming YiKongming Wu
May 20, 2020·Journal of Hematology & Oncology·Yonggui TianYi Zhang
Mar 17, 2019·International Journal of Molecular Sciences·Mohamed-Reda BenmebarekSebastian Kobold
Feb 18, 2020·Molecular Cancer·Jia-Qiao FanJianxun Song
Dec 3, 2020·Vaccines·Robert PytlikPavel Klener
Jun 5, 2021·Nature Biomedical Engineering·Stefanie LeschSebastian Kobold
Jun 6, 2021·Blood Cancer Journal·Franziska BlaeschkeTobias Feuchtinger
Aug 24, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nadia MensaliSébastien Wälchli

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Datasets Mentioned

BETA
Q9EP73

Methods Mentioned

BETA
fluorescence activated cell sorting
transgenic
flow cytometry
ELISA
Assay
enzyme linked immunosorbent assay
enzyme-linked immunosorbent assay

Software Mentioned

GraphPad Prism

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