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- W4313373478 abstract "Abstract Low frequency of tumor-specific T cells represents one major reason for failed immunotherapy. IL-2 can boost tumor-reactive T cells but its benefit is limited due to toxicity and potential off-target effects. We developed a novel IL-2/CD25 fusion protein which exhibits more favorable pharmacology when compared to IL-2. At low doses, IL-2/CD25 targets the high affinity IL-2R and selectively boosts Tregs. Here we show that a single administration of high dose mouse IL-2/CD25 in conjunction with cognate peptide and LPS amplified tumor-specific Pmel-1 CD8+ and TRP-1 CD4+ Teff cells and Pmel-1 memory cells while only transiently increasing Tregs. This approach led to effective anti-tumor responses against B16.F10 melanoma. This scheme was modified to amplify endogenous polyclonal melanoma-reactive T cells, which is translationally more relevant. Development of tumor-specific T cells required priming and boosting with a mixture of B16.F10 neoantigens and poly (I:C) followed by application of IL-2/CD25 after the boost. This resulted in largely a CD4+ anti-neoantigen specific T cell response. This immunization scheme delayed B16.F10 growth and extend survival time not only when immunized mice were challenged with B16.F10 but also for mice with pre-established B16.F10. The immune response within the tumor microenvironment was accompanied by increased frequencies of granzyme B-expressing CD4+ and CD8+ T cells. Our data show that limited application of high-dose IL-2/CD25 in the context of neoantigen vaccines offers potential advantages over IL-2 for melanoma treatment by avoiding toxicities seen with IL-2 therapy and minimizing Treg-associated tolerance." @default.
- W4313373478 created "2023-01-06" @default.
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- W4313373478 date "2020-05-01" @default.
- W4313373478 modified "2023-09-27" @default.
- W4313373478 title "Amplification of neoantigen-specific antitumor responses using a long-lasting IL-2 fusion protein" @default.
- W4313373478 doi "https://doi.org/10.4049/jimmunol.204.supp.239.9" @default.
- W4313373478 hasPublicationYear "2020" @default.
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