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Preface Throughout the last 20 years, progress in the field of molecular targeted therapies and genomics resulted in significant advances in the treatment of hematological and solid tumor malignancies. Nevertheless, the holy grail of cancer therapy, to transform this illness into a manageable chronic condition or cure it altogether, remains elusive. In spite of all the therapeutic advances made recently in cancer therapy, there is still a lack of adequate therapeutic approaches to manage cancer patients over long periods using conventional treatments. Therefore, the field of cancer vaccines or immunotherapies in general may provide a ray of hope for the future. Despite sustained research and development at both preclinical and clinical stages—in academic and industry settings for over two decades—there is still no approved therapeutic cancer vaccine in the United States. Promising preclinical data in a wide range of models still remain to be translated into innovative, safe, and effective therapeutic vaccines or active immunotherapies in cancer. It is the editors’ conviction that in light of the challenges associated with development of safe and effective cancer vaccines, it is more important to critically examine the failures, dissect past experience, and daringly challenge conventional paradigms that were artificially imported from other therapeutic areas of drug development. A translational approach (bench to bedside and reverse) aimed to optimize therapeutic platforms and guide the early development process to patient populations that would likely benefit most would require both significant time and financial commitment. However, this is a necessary evil for the success of not only cancer vaccines but also first-in-class molecular targeted therapies in general. Cancer Vaccines: Challenges and Opportunities in Translation addresses a wide range of readership from basic scientists with dual interest in oncology and immunology, translational scientists, clinical researchers, industry scientists, physicians, and technicians involved in the research and development of new v
vi Preface immunotherapies in cancer to business and project managers as well as regulatory experts within industry, academia, or government. The topic is approached from a different perspective by a panel of researchers in academia and industry involved with the development of major classes of cancer vaccines. The book outlines the gaps, challenges, and difficulties encountered in the past in conjunction with hurdles associated with translation of immunology research into clinic along with potential solutions that are currently implemented. The excitement related to the concept of cancer vaccination fueled a broad and diverse technology base currently in early or late clinical development. This created an impression of enormous activity in the field; nevertheless, due to the complexity and specificity of each of these platforms’ mechanisms of action along with the heterogeneous nature of the disease target, this assessment may be an overestimation. In fact, if one takes a critical perspective at this field, the more realistic assessment is that none of these technologies is close to be mature to yield a robust pipeline of drugs that would have the capability of making a significant impact in the current standard of cancer care. Nevertheless, we believe that far from having a pessimistic view of the field, this is rather a realistic, and in consequence, a constructive stance. The diverse technology base of cancer vaccines under development (categorized based on the nature of technology platform, in Table 1) reflects an ongoing quest for validating the proof of concept and building on approaches that have a potential to be applied across various cancers in a more economical fashion. This explains why cell-based and highly personalized approaches lead the way in clinical development and proof of concept generation. These are followed by synthetic, “off the shelf” approaches which are becoming more realistic with recent advances in cancer genomics and target discovery and validation. There are several key aspects that are emphasized in this book: (1) challenges presented by cancer vaccine development; (2) the relevance of preclinical models and basic science on new targets in translating new immunotherapies; (3) state of the art of current major cancer vaccines programs in development; (4) the importance of companion diagnostics and markers to the development of cancer vaccines; (5) new paradigms and models to optimize decision-making in the development of cancer vaccines; and (6) specific examples of failures and successes, along with take-home messages resulting from past experiences of developing cancer vaccines. In the first section of this book, dedicated to basic and preclinical research, Frédéric Lévy and his collaborators provide an in-depth perspective on the science underlying new cancer vaccine target discovery and evaluation, with an eye on tumor antigen processing, highlighting methods of optimizing current technologies in development and designing superior ones. In the subsequent chapter, Daniel L. Levey discusses preclinical models of cancer immunotherapy with emphasis on autologous (i.e., personalized) approaches along with value of these models in predicting outcomes in human disease. A critical analysis of the
Page 1 and 2: Translational Medicine Series 6 Can
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56 Srinivasan disease agents. Garda
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62 Srinivasan (69). In another stud
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84 Luptrawan et al. Dendritic cells
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104 Luptrawan et al. antigens (84,8
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108 Luptrawan et al. 66. Dunn GP, B
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7 Multimodality Immunization Approa
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Development of Novel Immunotherapeu
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206 Index Antigenic peptides degrad
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208 Index Chromogens, enzymatic act
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210 Index Freund’s adjuvants. See
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212 Index Langerhans cells, 133, 13
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214 Index [Peptide vaccines] invest
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216 Index TCRL. See TCR-like immuno
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Oncology and Immunology about the b
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