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- W4313368575 abstract "Abstract GVAX, a genetically modified whole cell vaccine, is thought to work by recruiting and activating APCs which then traffic to the draining lymph node and elicit tumor-specific T cells. GVAX has little therapeutic benefit as a monotherapy, but when combined with a Toll-like receptor (TLR) 4 adjuvant, TLR Enhanced GVAX (TEGVAX) significantly reduces tumor burden in mouse models. Paradoxically, the increased therapeutic benefit of TEGVAX corresponds with a decrease in delivery of tumor antigen to the dLN suggesting a different mechanism of tumor suppression than GVAX. To determine if TEGVAX alters the priming of CD8 T cells, we performed longitudinal studies of OT-1 CD8 T cell proliferation in vivo. GVAX induced rapid proliferation of OT-1 cells, whereas TEGVAX failed to induce any. We then determined if TEGVAX required myeloid or NK cells to function. TEGVAX reduced B16-mOVA tumor burden in NK depleted, but not myeloid cell depleted mice. To determine if T cell circulation from the dLN to the tumor was necessary, we administered FTY720, which sequesters circulating T cells in lymph nodes, prior to vaccination. TEGVAX significantly reduced B16-mOVA tumor growth even in the presence of FTY720 treatment, suggesting T cell priming was not required. Immune phenotyping of TEGVAX treated B16 tumors and showed the presence of activated tumor infiltrating tissue-resident memory (Trm) T cells. Our results demonstrate that combining a TLR4 agonist with GVAX completely alters the immune response to GVAX vaccination. TEGVAX primes naïve T cells poorly and does not require T cell circulation to reduce tumor growth. These findings suggest that TEGVAX functions by eliciting a tumor-specific Trm T cell response independent of lymph node priming." @default.
- W4313368575 created "2023-01-06" @default.
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- W4313368575 date "2020-05-01" @default.
- W4313368575 modified "2023-10-16" @default.
- W4313368575 title "TLR enhanced GVAX elicits tumor-specific tissue resident memory T cells independent of T cell priming" @default.
- W4313368575 doi "https://doi.org/10.4049/jimmunol.204.supp.246.28" @default.
- W4313368575 hasPublicationYear "2020" @default.
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