T-Cell Epitope Discovery for Therapeutic Cancer Vaccines

The success of recent immune checkpoint blockade trials in solid tumors has demonstrated the tremendous potential of immune-mediated treatment strategies for cancer therapy. These immune therapies activate preexisting cytotoxic CD8+ T cells (CTL) to selectively target and eradicate malignant cells. In vitro models suggest that these therapies may be more effective in combination with priming of CTL using cancer vaccines. CTL-mediated tumor targeting is achieved by its recognition of tumor antigenic epitopes presented on human leukocyte antigen (HLA) class I molecules by tumor cells. Discovering CTL-antigenic epitopes is therefore central to the design of therapeutic T-cell vaccines and immune monitoring of these complex immunotherapies. However, selecting and monitoring T-cell epitopes remains difficult due to the extensive polymorphism of HLA alleles and the presence of confounding non-immunogenic self-peptides. To overcome these challenges, this chapter presents methodologies for the design of CTL-targeted vaccines using selection of target HLA alleles, novel integrated computational strategies to predict HLA-class I CTL epitopes, and epitope validation methods using short-term ex vivo T-cell stimulation. This strategy results in the improved efficiency for selecting antigenic epitopes for CTL-mediated vaccines and for immune monitoring of tumor antigens.
Source: Springer protocols feed by Immunology - Category: Allergy & Immunology Source Type: news

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In the past decades, our knowledge about the relationship between cancer and the immune system has increased considerably. Recent years' success of cancer immunotherapy including monoclonal antibodies (mAbs), cancer vaccines, adoptive cancer therapy and the immune checkpoint therapy has revolutionized traditional cancer treatment. However, challenges still exist in this field. Personalized combination therapies via new techniques will be the next promising strategies for the future cancer treatment direction.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Immune-based therapy has emerged as a paradigm shift in cancer therapy with dramatic responses observed in previously incurable disease. Cancer vaccines are being developed to disrupt tumor-associated tolerance and activate and selectively expand tumor-specific lymphocytes within the native effector cell repertoire while maintaining immune-regulatory protection against autoimmunity. Although individual antigen approaches result in immune response with a suggestion of clinical effect in some settings, broader efficacy may be dependent on presentation of multiple antigens that capture clonal diversity presented in the contex...
Source: Blood - Category: Hematology Authors: Tags: Immunobiology and Immunotherapy, Review Articles, Review Series, Clinical Trials and Observations Source Type: research
CONCLUSION: ICOS/ICOS-L signal pathway has the potential to improve cancer treatment. However, studies in other models are needed to understand whether inhibition of ICOS expression or the blockage of its co-stimulation could be a potential therapeutic target or adjuvant treatment for immunotherapy. PMID: 29879883 [PubMed - as supplied by publisher]
Source: Current Protein and Peptide Science - Category: Biochemistry Authors: Tags: Curr Protein Pept Sci Source Type: research
In conclusion, EM-L2 displaying phage particles could be deemed as an encouraging strategy in contemporary cancer immunotherapy. PMID: 29908541 [PubMed - in process]
Source: Iranian Journal of Allergy, Asthma and Immunology - Category: Allergy & Immunology Authors: Tags: Iran J Allergy Asthma Immunol Source Type: research
Publication date: June 2018 Source:Molecular Immunology, Volume 98 Author(s): David Urbanavicius, Tara Alvarez, Georgina K. Such, Angus P.R. Johnston, Justine D. Mintern A complex and multifaceted relationship exists between cancer and the immune system. Advances in our understanding of this relationship have resulted in significant clinical attention in the possibilities of cancer immunotherapy. Harnessing the immune system’s potent and selective destructive capability is a major focus of attempts to treat cancer. Despite significant progress in the field, cancer therapy still remains significantly deficient, with ...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research
In the advent of Immune Checkpoint inhibitors (ICI) and of CAR-T adoptive T-cells, the new frontier in Oncology is Cancer Immunotherapy because of its ability to provide long term clinical benefit in metastati...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
li CA Abstract In recent years, cell-based therapies targeting the immune system have emerged as promising strategies for cancer treatment. This review summarizes manufacturing challenges related to production of antigen presenting cells as a patient-tailored cancer therapy. Understanding cell-material interactions is essential because in vitro cell culture manipulations to obtain mature antigen-producing cells can significantly alter their in vivo performance. Traditional antigen-producing cell culture protocols often rely on cell adhesion to surface-treated hydrophilic polystyrene flasks. More recent commercial ...
Source: Transfusion - Category: Hematology Authors: Tags: Transfusion Source Type: research
Scientists at the Vaccine and Immunotherapy Center (VIC) at Massachusetts General Hospital have uncovered a novel, two-agent immunotherapy combination that worked surprisingly well in animal models with malignant mesothelioma. The discovery has sparked new optimism for immunotherapy, which has struggled to provide consistently positive results with aggressive cancers such as mesothelioma. “This is the beginning of a new story of hope, a new combination of immunotherapy,” Dr. Mark Poznansky, director of the VIC and associate professor at Harvard Medical School, told Asbestos.com. “It worked quite well in a...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
In this study, we did not observe significant age-dependent upregulation of the prominent SASP cytokine Il6 in any tissue, although an upward trend was observed that was consistent in magnitude with previous observations in the heart and kidney. This modest age-related upward trend could be explained by a previous report which demonstrated that senescent cell-secreted IL-6 acts in an autocrine manner, reinforcing the senescent state, rather than inducing senescence or promoting dysfunction in neighboring cells. The decreased expression of Il6 with age we observed in the hypothalamus could be indicative of a lack or ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The Undoing Aging conference in Berlin is presently underway, a gathering of everyone who is anyone in the rejuvenation research community. It is hosted jointly by the SENS Research Foundation and the Forever Healthy Foundation, and is a unification of the varied themes of the past fifteen years of SENS conferences: the science of aging and its treatment from the earlier SENS conference series mixed with the industry, startup, and commercial development focus of the Rejuvenation Biotechnology series of recent years. The first rejuvenation therapies to be implemented and shown to work, those based on clearance of sen...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
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