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      Trial Watch: Peptide-based anticancer vaccines

      review-article
      1 , 2 , 3 , 1 , 2 , 3 , 4 , 1 , 2 , 3 , 1 , 2 , 5 , 6 , 2 , 5 , 6 , 2 , 6 , 7 , 8 , 8 , 9 , 10 , 1 , 11 , 2 , 3 , 8 , 10 , 12 , * , 1 , 2 , 3 , 8
      Oncoimmunology
      Taylor & Francis
      carbohydrate-mimetic peptides, immune checkpoint blockers, immunostimulatory cytokines, survivin, synthetic long peptides, WT1, APC, antigen-presenting cell, CMP, carbohydrate-mimetic peptide, FDA, Food and Drug Administration, EGFR, epidermal growth factor receptor, GM-CSF, granulocyte macrophage colony stimulating factor, HPV, human papillomavirus, IDH1, isocitrate dehydrogenase 1 (NADP+), soluble, IDO1, indoleamine 2, 3-dioxygenase 1, IFNα, interferon α, IL-2, interleukin-2, MUC1, mucin 1, NSCLC, non-small cell lung carcinoma, PADRE, pan-DR binding peptide epitope, PPV, personalized peptide vaccination, SLP, synthetic long peptide, TAA, tumor-associated antigen, TERT, telomerase reverse transcriptase, TLR, Toll-like receptor, TRA, tumor rejection antigen

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          Abstract

          Malignant cells express antigens that can be harnessed to elicit anticancer immune responses. One approach to achieve such goal consists in the administration of tumor-associated antigens (TAAs) or peptides thereof as recombinant proteins in the presence of adequate adjuvants. Throughout the past decade, peptide vaccines have been shown to mediate antineoplastic effects in various murine tumor models, especially when administered in the context of potent immunostimulatory regimens. In spite of multiple limitations, first of all the fact that anticancer vaccines are often employed as therapeutic (rather than prophylactic) agents, this immunotherapeutic paradigm has been intensively investigated in clinical scenarios, with promising results. Currently, both experimentalists and clinicians are focusing their efforts on the identification of so-called tumor rejection antigens, i.e., TAAs that can elicit an immune response leading to disease eradication, as well as to combinatorial immunostimulatory interventions with superior adjuvant activity in patients. Here, we summarize the latest advances in the development of peptide vaccines for cancer therapy.

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          Most cited references213

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions.

            DNA damage checkpoint genes, such as p53, are frequently mutated in human cancer, but the selective pressure for their inactivation remains elusive. We analysed a panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis. Progression to carcinoma was associated with p53 or 53BP1 inactivation and decreased apoptosis. A DNA damage response was also observed in dysplastic nevi and in human skin xenografts, in which hyperplasia was induced by overexpression of growth factors. Both lung and experimentally-induced skin hyperplasias showed allelic imbalance at loci that are prone to DNA double-strand break formation when DNA replication is compromised (common fragile sites). We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.
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              Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women

              The Lancet, 374(9686), 301-314
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                Author and article information

                Journal
                Oncoimmunology
                Oncoimmunology
                KONI
                Oncoimmunology
                Taylor & Francis
                2162-4011
                2162-402X
                9 January 2015
                April 2015
                : 4
                : 4
                : e974411
                Affiliations
                [1 ]Gustave Roussy Cancer Campus ; Villejuif, France
                [2 ]INSERM, U1138 ; Paris, France
                [3 ]Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Center de Recherche des Cordeliers ; Paris, France
                [4 ]Université Paris-Sud/Paris XI
                [5 ]Equipe 13; Center de Recherche des Cordeliers ; Paris, France
                [6 ]Université Pierre et Marie Curie/Paris VI ; Paris, France
                [7 ]Laboratory of Integrative Cancer Immunology, Center de Recherche des Cordeliers ; Paris, France
                [8 ]Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France
                [9 ]INSERM; U970 ; Paris, France
                [10 ]Pôle de Biologie; Hôpital Européen Georges Pompidou; AP-HP ; Paris, France
                [11 ]INSERM; U1015; CICBT507 ; Villejuif, France
                [12 ]Metabolomics and Cell Biology Platforms; Gustave Roussy Cancer Campus ; Villejuif, France
                Author notes
                [†]

                Equally contributed to this work.

                [‡]

                Share senior co-authorship.

                [* ]Correspondence to: Lorenzo Galluzzi; Email: eadoc@ 123456vodafone.it ; Guido Kroemer; Email: kroemer@ 123456orange.fr
                Article
                974411
                10.4161/2162402X.2014.974411
                4485775
                26137405
                615dc506-c826-4ff9-a498-c40d30632da7
                © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC© Jonathan Pol, Norma Bloy, Aitziber Buqué, Alexander Eggermont, Isabelle Cremer, Catherine Sautès-Fridman, Jerôme Galon, Eric Tartour, Laurence Zitvogel, Guido Kroemer, and Lorenzo Galluzzi

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 6 October 2014
                : 6 October 2014
                Page count
                Figures: 0, Tables: 1, References: 273, Pages: 12
                Categories
                Review

                Immunology
                carbohydrate-mimetic peptides,immune checkpoint blockers,immunostimulatory cytokines,survivin,synthetic long peptides,wt1,apc, antigen-presenting cell,cmp, carbohydrate-mimetic peptide,fda, food and drug administration,egfr, epidermal growth factor receptor,gm-csf, granulocyte macrophage colony stimulating factor,hpv, human papillomavirus,idh1, isocitrate dehydrogenase 1 (nadp+), soluble,ido1, indoleamine 2, 3-dioxygenase 1,ifnα, interferon α,il-2, interleukin-2,muc1, mucin 1,nsclc, non-small cell lung carcinoma,padre, pan-dr binding peptide epitope,ppv, personalized peptide vaccination,slp, synthetic long peptide,taa, tumor-associated antigen,tert, telomerase reverse transcriptase,tlr, toll-like receptor,tra, tumor rejection antigen

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