Dendritic cells in pancreatic cancer immunotherapy: vaccines and combination immunotherapies

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 patients with PC, DC vaccines have not yet fulfilled their promise. Additional strategies for combinatorial approaches aimed to augment and sustain the antitumor specific immune response elicited by DC vaccines are currently being investigated. Here, we will discuss DC vaccination immunotherapies that are currently under preclinical and clinical investigation and potential combination approaches for treating and improving the survival of PC patients.
Source: Pathology Research and Practice - Category: Pathology 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
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
Abstract No immunotherapy strategy is yet offering consistent results against Pancreatic ductal adenocarcinoma (PDAC). A randomized clinical trial testing repeated immunization with a Listeria monocytogenes-based vaccine encoding for mesothelin in combination with a GM-CSF-transfected allogeneic pancreatic cell vaccine reports no survival benefit for the vaccinated patients. PMID: 31315885 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionsFor the first time, a listeria vaccine-based immunotherapy was shown to be able to induce a tumor antigen-specific T cell response within the tumor microenvironment of a “cold” tumor such as PDAC and sensitize the tumor to checkpoint inhibitor therapy. Moreover, this combination immunotherapy led to objective tumor responses and survival benefit in the mice with spontaneously developed PDAC tumors. Therefore, our study supports developing Lm-ANXA2 as a therapeut ic agent in combination with anti-PD-1 antibody for PDAC treatment.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractPurpose of ReviewDespite all efforts, pancreatic ductal adenocarcinoma (PDAC) remains a disease that causes substantial morbidity and mortality, with a 5-year survival rate of 7%. Innovative paradigms for treating PDAC are urgently needed.Recent FindingsWe discuss the advances and difficulties in using immunotherapy and developing immunotherapeutic vaccines for PDAC. Current excitement about antigen-specific immunotherapy has been propelled by advances in multiple areas, such as next-generation sequencing to identify neoantigens and manufacturing to produce immunotherapeutic vaccines. Antigen-specific immunotherapy...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
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