Search results for "cancer vaccines"
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Harnessing Tumor Mutations for Truly Individualized Cancer Vaccines
2019
T cells are key effectors of anticancer immunity. They are capable of distinguishing tumor cells from normal ones by recognizing major histocompatibility complex–bound cancer-specific peptides. Accumulating evidence suggests that peptides associated with T cell–mediated tumor rejection arise predominantly from somatically mutated proteins and are unique to every patient's tumor. Knowledge of an individual's cancer mutanome (the entirety of cancer mutations) allows harnessing this enormous tumor cell–specific repertoire of highly immunogenic antigens for individualized cancer vaccines. This review outlines the preclinical and clinical state of individualized cancer vaccine development and t…
Short Peptide Vaccine Induces CD4+ T Helper Cells in Patients with Different Solid Cancers.
2015
Abstract Previous cancer vaccination trials often aimed to activate CD8+ cytotoxic T-cell (CTL) responses with short (8–10mer) peptides and targeted CD4+ helper T cells (TH) with HLA class II–binding longer peptides (12–16 mer) that were derived from tumor antigens. Accordingly, a study of immunomonitoring focused on the detection of CTL responses to the short, and TH responses to the long, peptides. The possible induction of concurrent TH responses to short peptides was widely neglected. In a recent phase I vaccination trial, 53 patients with different solid cancers were vaccinated with EMD640744, a cocktail of five survivin-derived short (9- or 10-mer) peptides in Montanide ISA 51VG. We m…
Targeting the Heterogeneity of Cancer with Individualized Neoepitope Vaccines
2015
Abstract Somatic mutations binding to the patient's MHC and recognized by autologous T cells (neoepitopes) are ideal cancer vaccine targets. They combine a favorable safety profile due to a lack of expression in healthy tissues with a high likelihood of immunogenicity, as T cells recognizing neoepitopes are not shaped by central immune tolerance. Proteins mutated in cancer (neoantigens) shared by patients have been explored as vaccine targets for many years. Shared (“public”) mutations, however, are rare, as the vast majority of cancer mutations in a given tumor are unique for the individual patient. Recently, the novel concept of truly individualized cancer vaccination emerged, which explo…
Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid.
2018
Abstract Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting immunologic memory. The mucin MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form expressed on healthy cells. Due to aberrant glycosylation in tumor cells, the specific peptide epitopes in its backbone are accessible and can be bound by antibodies induced by vaccination. Breast cancer patients develop per se only low levels of T cells and antibodies recognizing tumor-associated MUC1, and clinical trials with tumor-associated MUC1 yielded unsatisfac…
Translating nanoparticulate-personalized cancer vaccines into clinical applications: case study with RNA-lipoplexes for the treatment of melanoma
2016
The development of nucleic acid based vaccines against cancer has gained considerable momentum through the advancement of modern sequencing technologies and on novel RNA-based synthetic drug formats, which can be readily adapted following identification of every patient's tumor-specific mutations. Furthermore, affordable and individual ‘on demand’ production of molecularly optimized vaccines should allow their application in large groups of patients. This has resulted in the therapeutic concept of an active personalized cancer vaccine, which has been brought into clinical testing. Successful trials have been performed by intranodal administration of sterile isotonic solutions of synthetic …
Danger signals: Chemotherapy enhancers?
2017
IF 9.614; International audience; Endogenous danger signals are molecules normally present in a given cell compartment that are rapidly released following cell stress and induce immune responses. We and others have shown that dying tumor cells treated with some chemotherapies are able to induce anticancer immune responses, which rely on their release of danger signals such as the nuclear protein HMGB1. DNA can also be released from chemotherapy-treated tumor cells, act as a danger signal, and boost anticancer immunity. While the immunostimulatory properties of DNA have been identified for decades, the recent discovery of a novel family of receptors, cytosolic DNA sensors, has provided a nov…
CD19 Isoforms Enabling Resistance to CART-19 Immunotherapy Are Expressed in B-ALL Patients at Initial Diagnosis.
2017
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Immunotherapy of colorectal cancer: New perspectives after a long path
2016
Although significant therapeutic improvement has been achieved in the last 10 years, the survival of metastatic colorectal cancer patients remains in a range of 28 to 30 months. Presently, systemic treatment includes combination chemotherapy with oxaliplatin and/or irinotecan together with a backbone of 5-fluorouracil/levofolinate, alone or in combination with monoclonal antibodies to VEGFA (bevacizumab) or EGF receptor (cetuximab and panitumumab). The recent rise of immune checkpoint inhibitors in the therapeutic scenario has renewed scientific interest in the investigation of immunotherapy in metastatic colorectal cancer patients. According to our experience and view, here, we review the…
An RNA toolbox for cancer immunotherapy.
2018
Cancer immunotherapy has revolutionized oncology practice. However, current protein and cell therapy tools used in cancer immunotherapy are far from perfect, and there is room for improvement regarding their efficacy and safety. RNA-based structures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects and the ability to specifically bind different molecules. These functions make them versatile tools that may advance cancer vaccines and immunomodulation, surpassing existing approaches. These technologies should not be considered as competitors of current immunotherapies but as partners in synergistic combinations and as a clear opportunity to r…
Strategies in DNA vaccine for melanoma cancer
2020
According to reports of the international agency for cancer on research, although malignant melanoma shows less prevalence than nonmelanoma skin cancers, it is the major cause of skin cancer mortality. Given that, the production of effective vaccines to control melanoma is eminently required. In this regard, DNA-based vaccines have been extensively investigated for melanoma therapy. DNA vaccines are capable of inducing both cellular and humoral branches of immune responses. These vaccines possess some valuable advantages such as lack of severe side effects and high stability compared to conventional vaccination methods. The ongoing studies are focused on novel strategies in the development …