Tew / Fisher Advances in Cancer Research

1. Auflage 2014
ISBN: 978-0-12-800317-6
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 121, 426 Seiten

Reihe: Advances in Cancer Research

Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics. - Provides information on cancer research - Outstanding and original reviews - Suitable for researchers and students

Autoren/Hrsg.

Tew, Kenneth D.

Fisher, Paul B.

Leseproben

Chapter Two Therapeutic Cancer Vaccines
Jeffrey Schlom1; James W. Hodge; Claudia Palena; Kwong-Yok Tsang; Caroline Jochems; John W. Greiner; Benedetto Farsaci; Ravi A. Madan; Christopher R. Heery; James L. Gulley    Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
1 Corresponding author: email address: [e-mail] Abstract
Therapeutic cancer vaccines have the potential of being integrated in the therapy of numerous cancer types and stages. The wide spectrum of vaccine platforms and vaccine targets is reviewed along with the potential for development of vaccines to target cancer cell “stemness,” the epithelial-to-mesenchymal transition (EMT) phenotype, and drug-resistant populations. Preclinical and recent clinical studies are now revealing how vaccines can optimally be used with other immune-based therapies such as checkpoint inhibitors, and so-called nonimmune-based therapeutics, radiation, hormonal therapy, and certain small molecule targeted therapies; it is now being revealed that many of these traditional therapies can lyse tumor cells in a manner as to further potentiate the host immune response, alter the phenotype of nonlysed tumor cells to render them more susceptible to T-cell lysis, and/or shift the balance of effector:regulatory cells in a manner to enhance vaccine efficacy. The importance of the tumor microenvironment, the appropriate patient population, and clinical trial endpoints is also discussed in the context of optimizing patient benefit from vaccine-mediated therapy. Keywords Cancer vaccines Immunotherapy Clinical trials Animal models T cells Prostate cancer Tumor antigens 1 Introduction
This chapter encompasses the numerous factors involved in the design, development, and clinical application of therapeutic cancer vaccines both as a monotherapy and in combination with other forms of immunotherapy, as well as with nonimmune-based therapies. Among the topics discussed are (a) the wide spectrum of cancer vaccine targets; (b) the pros and cons of different vaccine platforms; (c) how animal models can be used, and should not be used, in vaccine development; (d) the influence of the tumor microenvironment and regulatory entities on vaccine efficacy; (e) how vaccine combination therapies with certain chemotherapeutic agents, radiation, hormone therapy, and small molecule targeted therapies and other immune therapeutics can potentially be used to enhance vaccine efficacy; (f) the appropriate patient populations and trial endpoints in vaccine clinical studies and the importance of tumor growth kinetics; and (g) the potential of new vaccines that can target cancer cell “stemness,” the epithelial-to-mesenchymal transition (EMT) phenotype, and drug resistance. While this chapter presents an overview of several aspects of therapeutic cancer vaccine development, many of the examples given are based on preclinical and clinical studies carried out at the National Cancer Institute, National Institutes of Health. Much of the information has been presented in previous review articles (Palena & Schlom, 2013; Schlom, 2012; Schlom, Hodge, et al., 2013; Schlom, Palena, et al., 2013) and/or in peer-reviewed publications as cited. 2 Cancer Vaccine Targets
The validity of a target for a therapeutic cancer vaccine will depend on the ability of a tumor cell to process the tumor-associated antigen (TAA) expressed by the vaccine in the context of a peptide–major histocompatibility complex (MHC) for T-cell recognition or on the surface of the tumor cell for B-cell recognition. The level of expression of the TAA in the tumor, the relative specificity of the TAA for tumor versus normal adult tissue, and the degree of inherent “tolerance” to the given TAA (Cheever et al., 2009; Gulley, Arlen, Hodge, & Schlom, 2010) are also of extreme importance. Common targets include oncofetal antigens, oncoproteins, differentiation-associated proteins, and viral proteins, among others (Table 2.1). The potential ideal target is a somatic point mutation that initiates and/or drives the neoplastic process. Clinical trials are underway to evaluate vaccines that target the various ras mutations found in colorectal and pancreatic cancer. However, large numbers of tumor-associated mutations among the various exons of the p53 suppressor gene, for example, make generating the large number of possible mutant p53 vaccines somewhat prohibitive. Similarly, it is also logistically difficult to develop vaccines to target the wide array of frameshift mutations and unique mutations that occur in individual tumors, which may differ among different tumor masses of the same patient. On the other hand, nonmutated oncoproteins can more easily be developed as targets; they include overexpressed HER2/neu (ERBB2), p53, and the C-terminal transmembrane subunit of mucin-1 (MUC-1), that is, MUC1-C (Kufe, 2009; Raina et al., 2011). Table 2.1 Spectrum of current and potential therapeutic cancer vaccine targets Target type Examples References Oncoprotein Point-mutated: ras, B-raf, frameshift mutations, undefined unique tumor mutations; HER2/neu, MUC-1 C-terminus, p53 Disis (2009), Salazar et al. (2009), Brichard and Lejeune (2008), Kufe (2009), Raina et al. (2011) Stem cell/EMT Brachyury, SOX-2, OCT-4, TERT, CD44high/CD24lo, CD133+ Polyak and Weinberg (2009), Dhodapkar et al. (2010), Dhodapkar and Dhodapkar (2011), Hua et al. (2011), Mine et al. (2009), Spisek et al. (2007), Fernando et al. (2010), Palena et al. (2007), Fernando et al. (2010) Oncofetal antigen CEA, MUC-1, MUC1-C Butts et al. (2005), Pejawar-Gaddy et al. (2010), Finn et al. (2011), Jochems et al. (2014) Cancer–testis MAGE-A3, BAGE, SEREX-defined, NY-ESO Karbach et al. (2011), Gnjatic et al. (2010), Gnjatic, Wheeler, et al. (2009), Hofmann et al. (2008) Tissue lineage PAP, PSA, gp100, tyrosinase, glioma antigen Schwartzentruber et al. (2011), Sosman et al. (2008), Kantoff, Schuetz, et al. (2010), Gulley, Arlen, Madan, et al. (2010), Kaufman et al. (2004), Kantoff, Higano, et al. (2010), Okada et al. (2011), Wheeler and Black (2011) Viral HPV, HCV Kemp et al. (2008, 2011) B-cell lymphoma Anti-id Schuster et al. (2011), Bendandi (2009), Inoges et al. (2006), Freedman et al. (2009) Antiangiogenic VEGF-R Kaplan et al. (2006), Xiang, Luo, Niethammer, and Reisfeld (2008), Frazer, Lowy, and Schiller (2007) Glycopeptides STn-KLH Gilewski et al. (2007), Ragupathi et al. (2009) BAGE, B melanoma antigen; CEA, carcinoembryonic antigen; EMT, epithelial–mesenchymal transition; gp100, glycoprotein 100; HCV, hepatitis C virus; HPV, human papillomavirus; MAGE-A3, melanoma-associated antigen-A3; MUC-1, mucin 1; NY-ESO, New York esophageal carcinoma antigen 1; OCT-4, octamer-binding transcription factor 4; PAP, prostatic acid phosphatase; PSA, prostate-specific antigen; SOX-2, (sex-determining region Y)-box-2; STn-KLH, sialyl-Tn-keyhole limpet hemocyanin; TERT, telomerase reverse transcriptase; VEGF-R, vascular endothelial growth factor receptor. Numerous trials have targeted “tissue lineage” antigens that are overexpressed in tumors and normally expressed in a nonvital organ, such as prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and the melanoma-associated antigens glycoprotein 100 (gp100) and tyrosinase. Numerous vaccine trials have also targeted a class of antigens categorized as oncofetal antigens, such as carcinoembryonic antigen (CEA), underglycosylated MUC-1, tumor-associated glycopeptides (Gilewski et al., 2007; Marshall et al., 2000; Ragupathi et al., 2009), and “cancer–testis” antigens defined by serological expression cloning (SEREX) immunodetection such as melanoma-associated antigen (MAGE-A3) and B melanoma antigen (BAGE) (Gnjatic, Old, & Chen, 2009; Gnjatic et al., 2010; Gnjatic, Wheeler, et al., 2009; Karbach et al., 2011). These antigens are overexpressed in many tumor types and to a lesser extent in some normal adult tissues. The recent approval by the U.S. Food and Drug Administration (FDA) of the Gardasil vaccine targeting the human papillomavirus (HPV) for the prevention of cervical cancer also renders HPV an attractive target for cervical cancer therapy, as does targeting the hepatitis C virus for liver cancer therapy. Preclinical studies have also shown the potential of vaccines that target molecules involved in tumor angiogenesis, such as the vascular endothelial growth factor receptor (VEGF-R) (Kaplan et al.,...