Combination of mAb-AR20.5, anti-PD-L1 and PolyICLC inhibits tumor progression and prolongs survival of MUC1.Tg mice challenged with pancreatic tumors

AbstractA 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, a ntibody 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 ce lls, 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 princ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Conditions:   Pancreatic Adenocarcinoma;   Pancreatic Cancer Intervention:   Biological: Autologous DC vaccine Sponsors:   Baylor College of Medicine;   Cancer Cures for Kids Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 17 October 2019Source: Pathology - Research and PracticeAuthor(s): Jia Yang, Junjie Shangguan, Aydin Eresen, Yu Lia, Jian Wang, Zhuoli ZhangAbstractDespite significant advances over the past decades of research, pancreatic cancer (PC) continues to have the worst 5-year survival of any malignancy. Dendritic cells (DCs) are the most potent professional antigen-presenting cells and are involved in the induction and regulation of antitumor immune responses. DC-based immunotherapy has been used in clinical trials for PC. Although safety, efficacy, and immune activation were reported in patient...
Source: Pathology Research and Practice - Category: Pathology Source Type: research
Abstract Despite significant advances over the past decades of research, pancreatic cancer (PC) continues to have the worst 5-year survival of any malignancy. Dendritic cells (DCs) are the most potent professional antigen-presenting cells and are involved in the induction and regulation of antitumor immune responses. DC-based immunotherapy has been used in clinical trials for PC. Although safety, efficacy, and immune activation were reported in patients with PC, DC vaccines have not yet fulfilled their promise. Additional strategies for combinatorial approaches aimed to augment and sustain the antitumor specific i...
Source: Pathology, Research and Practice - Category: Pathology Authors: Tags: Pathol Res Pract Source Type: research
A Wilmot Cancer Institute research team reports that combining a type of radiation therapy with immunotherapy not only cures pancreatic cancer in mice, but appears to reprogram the immune system to create an “immune memory” in the same way that a vaccine keeps the flu away.
Source: University of Rochester Medical Center Press Releases - Category: Universities & Medical Training Authors: Source Type: news
AbstractPancreatic cancer has been termed a ‘recalcitrant cancer’ due to its relative resistance to chemotherapy and immunotherapy. This resistance is thought to be due in part to the dense fibrotic tumor microenvironment and lack of tumor infiltrating CD8 + T cells. The gastrointestinal peptide, gastrin, has been shown to stimulate g rowth of pancreatic cancer by both a paracrine and autocrine mechanism. Interruption of gastrin at the CCK receptor may reduce tumor-associated fibrosis and alter tumor immune cells. Polyclonal Ab Stimulator (PAS) is a vaccine that targets gastrin and has been shown ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
This study suggests that inhibition of the cancer promoting effects of gastrin in pancreatic cancer can decrease metastases by altering the tumor microenvironment (TME) and decreasing pathways that activate the epithelial mesenchymal transition (EMT). PAS vaccine appears to change the tumor microenvironment, making it more susceptible to therapy with an immune checkpoint antibody. This novel combination of two immunotherapies may improve survival of pancreatic cancer by decreasing both tumor growth and metastasis formation. PMID: 31433212 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Patients with mesothelioma are now eligible for a multicancer clinical trial studying the effectiveness of personalized immunotherapy at the University of California, San Diego Medical Center. The phase I clinical trial involves a combination of Keytruda (pembrolizumab), a proven immunotherapy drug, and an individualized vaccine based upon the genetic mutations found in each patient’s cancer. “This is the future of cancer treatment,” Dr. Ezra Cohen, principal investigator and director of the San Diego Center for Precision Immunotherapy, told The Mesothelioma Center at Asbestos.com. “Now, we still ha...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Abstract CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 antibodies of varying formulations have been evaluated in the clinic and found to be tolerable and feasible. Administration is associated with mild to moderate (but transient) cytokine release syndrome, readily managed in the outpatient setting. Antitumor activity with or without anti-CTLA4 monoclonal antibody (mAb) therapy has been observed in patients with m...
Source: Annual Review of Medicine - Category: General Medicine Authors: Tags: Annu Rev Med Source Type: research
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