We are analyzing https://link.springer.com/article/10.1007/s00262-023-03433-3.

Title:
Factors impacting the efficacy of the in-situ vaccine with CpG and OX40 agonist | Cancer Immunology, Immunotherapy
Description:
Background The in-situ vaccine using CpG oligodeoxynucleotide combined with OX40 agonist antibody (CpG + OX40) has been shown to be an effective therapy activating an anti-tumor T cell response in certain settings. The roles of tumor volume, tumor model, and the addition of checkpoint blockade in the efficacy of CpG + OX40 in-situ vaccination remains unknown. Methods Mice bearing flank tumors (B78 melanoma or A20 lymphoma) were treated with combinations of CpG, OX40, and anti-CTLA-4. Tumor growth and survival were monitored. In vivo T cell depletion, tumor cell phenotype, and tumor infiltrating lymphocyte (TIL) studies were performed. Tumor cell sensitivity to CpG and macrophages were evaluated in vitro. Results As tumor volumes increased in the B78 (one-tumor) and A20 (one-tumor or two-tumor) models, the anti-tumor efficacy of the in-situ vaccine decreased. In vitro, CpG had a direct effect on A20 proliferation and phenotype and an indirect effect on B78 proliferation via macrophage activation. As A20 tumors progressed in vivo, tumor cell phenotype changed, and T cells became more involved in the local CpG + OX40 mediated anti-tumor response. In mice with larger tumors that were poorly responsive to CpG + OX40, the addition of anti-CTLA-4 enhanced the anti-tumor efficacy in the A20 but not B78 models. Conclusions Increased tumor volume negatively impacts the anti-tumor capability of CpG + OX40 in-situ vaccine. The addition of checkpoint blockade augmented the efficacy of CpG + OX40 in the A20 but not B78 model. These results highlight the importance of considering multiple preclinical model conditions when assessing the efficacy of cancer immunotherapy regimens and their translation to clinical testing.
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tumor, cpg, tumors, mice, fig, cells, pubmed, cell, antitumor, article, model, response, large, cancer, small, google, scholar, treated, local, models, survival, untreated, cas, data, antictla, immunotherapy, volume, insitu, effect, size, preclinical, distant, immune, significantly, vaccine, shown, efficacy, twotumor, progression, treatment, central, systemic, expression, calculated, average, pbs, bearing, macrophages, experiments, significant,

Topics {✒️}

t-cell-inflamed tumor microenvironment cpg + ox40 + cd4 depletion + cd8 depletion emerging evidence suggest article download pdf cd45 + /cd3 + /cd4 + /cd25 + /foxp3 + myeloid-derived suppressor cells triplicate wells ± standard error delivering intra-tumor injectables tnfr-related molecule ox40 cytotoxic t-cell response increasing ifn-γ expression [3h]thymidine incorporation assay strong anti-tumor response anti-tumor immune response strongest anti-tumor effect significant anti-tumor response direct anti-proliferative effects enhanced anti-tumor response significant anti-tumor effect intra-experimental media average systemic anti-tumor response time-weighted average analysis full size image local anti-tumor response tumor-curing immune response systemic anti-tumor effect systemic anti-tumor effects integrated dna technologies local anti-tumor effect t-cell modulation combined cpg + ox40 + rat igg cpg + ox40 + anti-ctla-4 cpg + ox40 cures mice macrophage anti-tumor effect depleting tumor-specific tregs concomitant immune tolerance cpg + ox40 lost effectiveness situ vaccine cpg + ox40 predict therapy response privacy choices/manage cookies tumor-specific inhibition sagiv-barfi immune checkpoint blockade cpg increases immune data suggest cpg + ox40 related subjects full access tumor burden increases flow cytometry analysis checkpoint blockade augmented

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Adams CP, Brantner VV (2006) Estimating the cost of new drug development: is it really 802 million dollars?

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         headline:Factors impacting the efficacy of the in-situ vaccine with CpG and OX40 agonist
         description:The in-situ vaccine using CpG oligodeoxynucleotide combined with OX40 agonist antibody (CpG + OX40) has been shown to be an effective therapy activating an anti-tumor T cell response in certain settings. The roles of tumor volume, tumor model, and the addition of checkpoint blockade in the efficacy of CpG + OX40 in-situ vaccination remains unknown. Mice bearing flank tumors (B78 melanoma or A20 lymphoma) were treated with combinations of CpG, OX40, and anti-CTLA-4. Tumor growth and survival were monitored. In vivo T cell depletion, tumor cell phenotype, and tumor infiltrating lymphocyte (TIL) studies were performed. Tumor cell sensitivity to CpG and macrophages were evaluated in vitro. As tumor volumes increased in the B78 (one-tumor) and A20 (one-tumor or two-tumor) models, the anti-tumor efficacy of the in-situ vaccine decreased. In vitro, CpG had a direct effect on A20 proliferation and phenotype and an indirect effect on B78 proliferation via macrophage activation. As A20 tumors progressed in vivo, tumor cell phenotype changed, and T cells became more involved in the local CpG + OX40 mediated anti-tumor response. In mice with larger tumors that were poorly responsive to CpG + OX40, the addition of anti-CTLA-4 enhanced the anti-tumor efficacy in the A20 but not B78 models. Increased tumor volume negatively impacts the anti-tumor capability of CpG + OX40 in-situ vaccine. The addition of checkpoint blockade augmented the efficacy of CpG + OX40 in the A20 but not B78 model. These results highlight the importance of considering multiple preclinical model conditions when assessing the efficacy of cancer immunotherapy regimens and their translation to clinical testing.
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      name:Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, USA
      name:Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, USA
      name:Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, USA
      name:4159 MACC Fund UW Childhood Cancer Research Wing, Wisconsin Institute for Medical Research, University of Wisconsin, Madison, USA

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