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Title:
Combination of mAb-AR20.5, anti-PD-L1 and PolyICLC inhibits tumor progression and prolongs survival of MUC1.Tg mice challenged with pancreatic tumors | Cancer Immunology, Immunotherapy
Description:
A substantial body of evidence suggests the existence of MUC1-specific antibodies and cytotoxic T cell activities in pancreatic cancer patients. However, tumor-induced immunosuppression renders these responses ineffective. The current study explores a novel therapeutic combination wherein tumor-bearing hosts can be immunologically primed with their own antigen, through opsonization with a tumor antigen-targeted antibody, mAb-AR20.5. We evaluated the efficacy of immunization with this antibody in combination with PolyICLC and anti-PD-L1. The therapeutic combination of mAb-AR20.5 + anti-PD-L1 + PolyICLC induced rejection of human MUC1 expressing tumors and provided a long-lasting, MUC1-specific cellular immune response, which could be adoptively transferred and shown to provide protection against tumor challenge in human MUC1 transgenic (MUC.Tg) mice. Furthermore, antibody depletion studies revealed that CD8 cells were effectors for the MUC1-specific immune response generated by the mAb-AR20.5 + anti-PD-L1 + PolyICLC combination. Multichromatic flow cytometry data analysis demonstrated a significant increase over time in circulating, activated CD8 T cells, CD3+CD4−CD8−(DN) T cells, and mature dendritic cells in mAb-AR20.5 + anti-PD-L1 + PolyICLC combination-treated, tumor-bearing mice, as compared to saline-treated control counterparts. Our study provides a proof of principle that an effective and long-lasting anti-tumor cellular immunity can be achieved in pancreatic tumor-bearing hosts against their own antigen (MUC1), which can be further potentiated using a vaccine adjuvant and an immune checkpoint inhibitor.
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Keywords {🔍}
pubmed, article, cancer, google, scholar, cas, cells, central, pancreatic, tumor, muc, immune, immunol, human, immunity, res, cell, polyiclc, antibody, combination, antipdl, mice, gamma, mabar, hollingsworth, patients, clin, immunotherapy, muctg, tumors, schultes, mucspecific, access, delta, tcell, immunother, blockade, usa, privacy, cookies, content, immunology, responses, dendritic, vaccine, lymphocytes, type, therapy, data, publish,
Topics {✒️}
5 + anti-pd-l1 + polyiclc induced rejection 5 + anti-pd-l1 + polyiclc combination-treated granulocyte-macrophage colony-stimulating factor month download article/chapter anti-pd-1/pd-l1 therapy muc1-anti-muc1 immune complexes 5 + anti-pd-l1 + polyiclc combination anti-pd-l1 antibody ige antibody-dependent surveillance pd-1/pd-l1 blockade anti-muc1 monoclonal antibody anti-muc1 antibody as1402 listeria monocytogenes-expressing mesothelin immunotherapy t-cell function tumor-induced immunosuppression renders saline-treated control counterparts tumor-selective monoclonal antibody tumor antigen-targeted antibody muc1-specific tumor immunity human leukocyte antigen–antigen pancreatic tumor-bearing hosts anti-pd-l1 cd3+cd4−cd8− cd3+ cd4−cd8− article cancer immunology cellular antitumor immunity full article pdf t-cell exhaustion antitumor activity mediated vaccines immune complexes diaz la jr muc1-specific antibodies alpha-galactosylceramide-loaded tumor-specific immunity privacy choices/manage cookies human muc1 transgenic mhc class tumor cell type tlr3 ligand poly tumor-bearing hosts related subjects immune checkpoint blockade polyinosinic-polycytidylic acid invariant natural killer muc1 transgenic mice immune checkpoint inhibitor prevent immune decline cd19 antibodies assessed article mehla tumor-bearing mice
Questions {❓}
- D’Acquisto F, Crompton T (2011) CD3+ CD4−CD8−(double negative) T cells: saviours or villains of the immune response?
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headline:Combination of mAb-AR20.5, anti-PD-L1 and PolyICLC inhibits tumor progression and prolongs survival of MUC1.Tg mice challenged with pancreatic tumors
description:A substantial body of evidence suggests the existence of MUC1-specific antibodies and cytotoxic T cell activities in pancreatic cancer patients. However, tumor-induced immunosuppression renders these responses ineffective. The current study explores a novel therapeutic combination wherein tumor-bearing hosts can be immunologically primed with their own antigen, through opsonization with a tumor antigen-targeted antibody, mAb-AR20.5. We evaluated the efficacy of immunization with this antibody in combination with PolyICLC and anti-PD-L1. The therapeutic combination of mAb-AR20.5 + anti-PD-L1 + PolyICLC induced rejection of human MUC1 expressing tumors and provided a long-lasting, MUC1-specific cellular immune response, which could be adoptively transferred and shown to provide protection against tumor challenge in human MUC1 transgenic (MUC.Tg) mice. Furthermore, antibody depletion studies revealed that CD8 cells were effectors for the MUC1-specific immune response generated by the mAb-AR20.5 + anti-PD-L1 + PolyICLC combination. Multichromatic flow cytometry data analysis demonstrated a significant increase over time in circulating, activated CD8 T cells, CD3+CD4−CD8−(DN) T cells, and mature dendritic cells in mAb-AR20.5 + anti-PD-L1 + PolyICLC combination-treated, tumor-bearing mice, as compared to saline-treated control counterparts. Our study provides a proof of principle that an effective and long-lasting anti-tumor cellular immunity can be achieved in pancreatic tumor-bearing hosts against their own antigen (MUC1), which can be further potentiated using a vaccine adjuvant and an immune checkpoint inhibitor.
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PolyICLC
Anti-PD-L1
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MUC1
Pancreatic cancer
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Cancer Research
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headline:Combination of mAb-AR20.5, anti-PD-L1 and PolyICLC inhibits tumor progression and prolongs survival of MUC1.Tg mice challenged with pancreatic tumors
description:A substantial body of evidence suggests the existence of MUC1-specific antibodies and cytotoxic T cell activities in pancreatic cancer patients. However, tumor-induced immunosuppression renders these responses ineffective. The current study explores a novel therapeutic combination wherein tumor-bearing hosts can be immunologically primed with their own antigen, through opsonization with a tumor antigen-targeted antibody, mAb-AR20.5. We evaluated the efficacy of immunization with this antibody in combination with PolyICLC and anti-PD-L1. The therapeutic combination of mAb-AR20.5 + anti-PD-L1 + PolyICLC induced rejection of human MUC1 expressing tumors and provided a long-lasting, MUC1-specific cellular immune response, which could be adoptively transferred and shown to provide protection against tumor challenge in human MUC1 transgenic (MUC.Tg) mice. Furthermore, antibody depletion studies revealed that CD8 cells were effectors for the MUC1-specific immune response generated by the mAb-AR20.5 + anti-PD-L1 + PolyICLC combination. Multichromatic flow cytometry data analysis demonstrated a significant increase over time in circulating, activated CD8 T cells, CD3+CD4−CD8−(DN) T cells, and mature dendritic cells in mAb-AR20.5 + anti-PD-L1 + PolyICLC combination-treated, tumor-bearing mice, as compared to saline-treated control counterparts. Our study provides a proof of principle that an effective and long-lasting anti-tumor cellular immunity can be achieved in pancreatic tumor-bearing hosts against their own antigen (MUC1), which can be further potentiated using a vaccine adjuvant and an immune checkpoint inhibitor.
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PolyICLC
Anti-PD-L1
CD8 T cells
MUC1
Pancreatic cancer
Oncology
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