PF-06940434
PF-06940434 (ADWA-11) is a monoclonal antibody targeting integrin αvβ8. PF-06940434 inhibits αvβ8-mediated TGF-β activation. PF-06940434 increases the accumulation of tumor-infiltrating CD8+ T cells and upregulates the expression of granzyme B and TNF-γ. PF-06940434 blocks the inhibitory effect of CD4+CD25+ T cells on the cytotoxic activity of tumor CD8+ T cells. PF-06940434 enhances the anti-tumor efficacy of combination therapies with other immunomodulators or radiotherapy and induces long-term anti-tumor immunity. PF-06940434 can be used in the research of squamous cell carcinoma, breast cancer, colon cancer, and prostate adenocarcinoma.
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Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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αvβ8 |
PF-06940434 (0.067-66.67 pM) potently inhibits αvβ8-mediated cell adhesion to TGF-β1 latency-associated peptide in SNB19 human glioblastoma cells[1].
PF-06940434 (0.067-66.67 pM; 16 h) potently blocks αvβ8-mediated TGF-β activation in a co-culture system of SNB229 human glioblastoma cells and TMLC reporter cells[1].
PF-06940434 (48 h) blocks the suppressive effect of TRAMPC2 tumor-derived CD25+/CD4+ T cells on CD8+ T cell-mediated TRAMPC2 tumor cell killing in a 48-hour in vitro co-culture assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PF-06940434 (10 mg/kg; i.p.; days 0 and 7) monotherapy induces complete tumor regression in 10% of mice with mammary carcinoma, enhances intratumoral CD8+ T cell cytotoxic function, inhibits TGF-β signaling, and elicits long-term anti-tumor immunity[1].
PF-06940434 (10 mg/kg; i.p.; days 0 and 7) monotherapy potently inhibits prostate adenocarcinoma tumor growth, increases intratumoral CD8+ T cell accumulation and cytotoxic gene expression, and inhibits TGF-β signaling[1].
PF-06940434 (10 mg/kg; i.p.; days 0 and 7) inhibits prostate adenocarcinoma tumor growth and improves survival in wild-type littermate mice, with no additive effect in mice with T cell-specific Itgb8 deletion[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:FVB/NJ (equal numbers of male and female; subcutaneous injection of 1.5×104 CCK168 cells to induce squamous cell carcinoma)[1]
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Dosage:10 mg/kg
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Administration:i.p.; days 0 and 7
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Result:Induced tumor regression in most mice, with 4 of 10 mice showing complete tumor regression.
Significantly increased the percentage of intratumoral CD8+ T cells, the percentage of CD8+ T cells expressing granzyme B, and the percentage of CD4+ and CD8+ T cells expressing interferon-γ (IFNγ).
Significantly reduced SMAD3 phosphorylation (pSMAD3) in whole-tumor lysates.
Significantly upregulated mRNA expression of granzyme B, IFNγ, and Fas ligand in intratumoral CD8+ T cells.
Prevented tumor formation in re-challenged mice, indicating long-term anti-tumor immunity.
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Animal Model:BALB/c (female; orthotopic injection of 5×104 EMT6 cells into the fourth mammary fat pad to induce mammary carcinoma)[1]
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Dosage:10 mg/kg
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Administration:i.p.; days 0 and 7
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Result:Induced complete tumor regression in 2 of 20 mice.
Significantly increased the percentage of intratumoral CD8+ T cells, the percentage of CD8+ T cells expressing granzyme B, and the percentage of CD4+ and CD8+ T cells expressing IFNγ.
Significantly reduced pSMAD3 in whole-tumor lysates.
Significantly upregulated mRNA expression of granzyme B, IFNγ, granzyme A, and Fas ligand in intratumoral CD8+ T cells.
Prevented tumor formation in re-challenged mice, indicating long-term anti-tumor immunity.
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Animal Model:C57BL/6J (male; subcutaneous injection of 1×106 TRAMPC2 cells with matrigel to induce prostate adenocarcinoma)[1]
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Dosage:10 mg/kg
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Administration:i.p.; days 0 and 7
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Result:Markedly reduced tumor growth.
Significantly increased the percentage of intratumoral CD8+ T cells, the percentage of CD8+ T cells expressing granzyme B, and the percentage of CD4+ and CD8+ T cells expressing IFNγ.
Significantly reduced pSMAD3 in whole-tumor lysates.
Significantly upregulated mRNA expression of granzyme B, IFNγ, granzyme A, and Fas ligand in intratumoral CD8+ T cells.
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Animal Model:C57BL/6J (male, Itgb8-f/f littermates; subcutaneous injection of 1×106 TRAMPC2 cells with matrigel to induce prostate adenocarcinoma)[1]
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Dosage:10 mg/kg
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Administration:i.p.; days 0 and 7
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Result:Significantly inhibited tumor growth and enhanced survival in Itgb8-f/f littermates.
Showed no additional benefit in CD4-Cre;Itgb8-f/f mice (with T cell-specific Itgb8 deletion).
Chemical Information
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SMILES
[PF-06940434]
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Synonyms
ADWA-11
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PF-06940434 Related Classifications
HY-P992519 Related Classifications
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