CD40 Agonist Antibodies in Cancer Immunotherapy.

CD40 Agonist Antibodies in Cancer Immunotherapy. Annu Rev Med. 2019 Aug 14;: Authors: Vonderheide RH 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 melanoma, and major tumor regressions have been observed in patients with pancreatic cancer, mesothelioma, and other tumors in combination with chemotherapy. In a recent study of chemotherapy plus CD40 mAb, with or without PD-1 mAb, the objective response rate in patients with untreated, metastatic pancreatic cancer was>50%. Mechanistically, the combination of chemotherapy followed by CD40 mAb functions as an in situ vaccine; in addition, destruction of stroma by CD40-activated macrophages may enhance chemotherapy delivery. Evidence to date suggests that CD40 activation is a critical and nonredundant mechanism to convert so-called cold tumors to hot ones (with prominent tumor infiltration of T cells), sensitizing them to checkpoint inhibition. ...
Source: Annual Review of Medicine - Category: General Medicine Authors: Tags: Annu Rev Med Source Type: research

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Ribonucleases (RNases) are a large number of enzymes gathered into different bacterial or eukaryotic superfamilies. Bovine pancreatic RNase A, bovine seminal BS-RNase, human pancreatic RNase 1, angiogenin (RNase 5), and amphibian onconase belong to the pancreatic type superfamily, while binase and barnase are in the bacterial RNase N1/T1 family. In physiological conditions, most RNases secreted in the extracellular space counteract the undesired effects of extracellular RNAs and become protective against infections. Instead, if they enter the cell, RNases can digest intracellular RNAs, becoming cytotoxic and having advanta...
Source: Frontiers in Immunology - Category: Allergy & Immunology 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
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Source: JAMA Surgery - Category: Sports Medicine Source Type: research
This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Joe Abdo1, Christopher S. Wichman2, Nicholas E. Dietz1,3, Pawel Ciborowski4, John Fleegel1, Sumeet K. Mittal1,5 and Devendra K. Agrawal1* 1Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States 2Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States 3Department of Pathology, CHI Health Creighton University Medical Center, College of Medicine, Omaha, NE, United States 4Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE, United States 5Norton Thoracic Institute, St....
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study aimed to explore whether a correlation exists between the incidence and mortality of cancers and normalized internet search volumes on the big data platform, Baidu. We also assessed whether the distribution of people who searched for specific types of cancer differed by gender. Finally, we determined whether there were regional disparities among people who searched the Web for cancer-related information. Methods: Standard Boolean operators were used to choose search terms for each type of cancer. Spearman’s correlation analysis was used to explore correlations among monthly search index values for each can...
Source: Journal of Medical Internet Research - Category: General Medicine Authors: Source Type: research
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Source: Cancer Causes and Control - Category: Cancer & Oncology Source Type: research
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Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
AbstractSeveral distinct melanoma syndromes have been defined, and genetic tests are available for the associated causative genes. Guidelines for melanoma genetic testing have been published as an informal “rule of twos and threes,” but these guidelines apply toCDKN2A testing and are not intended for the more recently described non-CDKN2A melanoma syndromes. In order to develop an approach for the full spectrum of hereditary melanoma patients, we have separated melanoma syndromes into two types: “melanoma dominant” and “melanoma subordinate.” Syndromes in which melanoma is a predominant ...
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research
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