HANDBOOK OF CANCER VACCINES

CANCER DRUG DISCOVERY AND DEVELOPMENT

BEVERLY A. TEICHER, SERIES EDITOR

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HANDBOOK OF

CANCER VACCINES

Edited by

MICHAEL A. MORSE, MD

TIMOTHY M. CLAY, PhD

H. KIM LYERLY, MD

Duke University Medical Center Durham, NC

H UMANA PRESS TOTOWA, NEW JERSEY

© 2004 Humana Press Inc.

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Due diligence has been taken by the publishers, editors, and authors of this book to assure the accuracy ofthe information published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord with the standards accepted at the time of publication. Notwithstanding, as new research, changes in government regulations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occurs, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications. This is of utmost importance when the recommended drug herein is a new or infrequently used drug. It is the responsibility of the treating physician to determine dosages and treatment strategies for individual patients. Further it is the responsibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in their clinical practice. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences from the application of the information presented in this book and make no warranty, express or implied, with respect to the contents in this publication.

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ISBN 978-1-4684-9818-9 ISBN 978-1-59259-680-5 (eBook) DOI 10.1007/978-1-59259-680-5

Library of Congress Cataloging-in-Publication Data

Handbook of cancer vaccines 1 edited by Michael A. Morse, Timothy M. Clay, H. Kim Lyerly.

p. ; cm. -- (Cancer drug discovery and development) Includes bibliographical references and index. I. Cancer vaccines--Handbooks, manuals, etc. [DNLM: I. Cancer Vaccines. QZ 266 H236 2003] I. Morse, Michael A.

II. Clay, Timothy M. III. Lyerly, H. Kim. IV. Series. RC271.I45H36 2003 616.99'406--dc21

2003011110

ACKNOWLEDGMENTS

To Emy, Carla, and Annie, for their support and understanding To Shubi, Allyson, John, and Teresa, for their dedication to patient care and safety To our research staff, for their perseverance and thirst for discovery To Karen, for her tireless commitment to this project To our patients, who courageously participate in our search for a cure

v

PREFACE

Harnessing the immune system to destroy tumors has undeniable appeal. Current cytotoxic cancer therapies are relatively indiscriminate, with narrow therapeutic win­dows. Immune effectors have the capacity to precisely target cells for destruction. Cytotoxic therapies often fail because of tumor cell resistance. The immune system can adapt to ever-changing challenges. Cytotoxic therapies are viewed as poisons, whereas immune-mediated cell death is viewed as natural.

The immune system has two arms, cellular and humoral, and each immunotherapy can be broadly described by which arm mediates its activity. Immunotherapies can also be classified by whether they acti vate immune effectors or involve their passi ve transfer. For example, active immunotherapy involves immunization to activate T cell or antibody responses in vivo, whereas passive immunotherapy involves the infusion of T cells or antibodies activated or generated ex vivo. Although the most commercially successful products thus far have been monoclonal antibodies administered intravenously, animal models have suggested that immunizations can be used to protect against tumor challenge and more importantly, to destroy established tumors. Over the last two decades, the identification of antigens that can serve as targets for immune effectors and the elucida­tion of the mechanisms for activating antigen-specific immune responses have resulted in a profusion of strategies for activating tumor antigen-specific immune responses. These so-called therapeutic vaccines, unlike prophylactic vaccines for the prevention of infections, all share some basic attributes, the presence of target antigens, and a method for delivering the antigen into the antigen-presentation machinery in conjunction with other molecules required to provide T - and/or B-cell activation.

The Handbook of Cancer Vaccines is intended to provide a comprehensive description of the scientific background for therapeutic vaccines, the challenges to their develop­ment, and their current use to treat cancer. After an overview of the immune response to cancer vaccines, this text will describe methods of antigen discovery followed by indi­vidual chapters on basic issues regarding all vaccines, such as immune adjuvants and prime-boost strategies. Subsequently, chapters will be devoted to the scientific basis and pre-clinical development of the major vaccine strategies, such as peptide, tumor cell, and dendritic cell vaccines. The last half of the text describes the clinical results for cancer vaccines used to treat many of the common cancers. Finally, chapters are devoted to the monitoring of biologic responses to vaccines and to statistical and regulatory issues affecting the design and conduct of clinical trials of cancer vaccines.

vii

Michael A. Morse, MD

Timothy M. Clay, PhD

H. Kim Lyerly, MD

CONTENTS

Acknowledgments ........... : .............................................................................................. v

Preface....................................................................................................................... .. vii

Contributors ................................................................................................................ xiii

Value-Added eBook/PDA ........................................................................................ xvii

PART I: BASIC SCIENCE OF TUMOR ANTIGENS AND IMMUNE ACTIVATION

1 Biology of the Cancer Vaccine Immune Response ............................................. 3 Michael A. Morse, Timothy M. Clay, and H. Kim Lyerly

2 The Rational Design of T-Cell Epitopes With Enhanced Immunogenicity ..... 11 John Fikes

3 Identification of Tumor Antigens Using Subtraction and Microarrays ............ 19 Jiangchun Xu

4 Tumor Antigen Discovery With T Cells ............................................................ 31 Paul F. Robbins

5 Targeting Viral Antigens for the Treatment of Malignancies ........................... 49 Gretchen L. Eiben, Diane M. Da Silva, Steven C. Fausch,

Amanda M. Krier, I. Caroline Le Poole, Megan E. Papineau, Michael I. Nishimura, and W. Martin Kast

6 Immune Defects in Cancer ................................................................................. 65 Dmitry Gabrilovich and Vladimir Pisarev

7 Escape of Tumors From the Immune System: Role of the Transforming Growth Factor-f3-Signaling Pathway ................... 85 Gerard C. Blobe

PART II: GENERAL VACCINE AND IMMUNOTHERAPY STRATEGIES

8 Immune Adjuvants ............................................................................................. 99 Jory R. Baldridge, Susan Hand Zimmermann, and Sally P. Mossman

9 Heterologous Prime-Boost Vaccination in Tumor Immunotherapy ............... 115 Michael J. Palmowski and Caroline Smith

10 Peptide-Based Vaccines ................................................................................... 121 Carmen M. Berger, Keith L. Knutson, Lupe G. Salazar,

Kathy Schiffman, and Mary L. Disis

11 Antibody-Inducing Cancer Vaccines Against Cell-Surface Carbohydrate Antigens .............................................. 137 Govind Ragupathi, John Gathuru, and Philip O. Livingston

12 Anti-Idiotype Vaccines ..................................................................................... 157 Sunil K. Chatterjee, Malaya Bhattacharya-Chatterjee,

and Kenneth A. Foon ix

x Contents

13 Pox Viral Vaccines ........................................................................................... 175 James L. Gulley, Philip M. Arlen, and Jeffrey Schlom

14 Utility of Adenovirus-Based Vectors for Multiple Cancer Vaccine Approaches .................................................... 193 Zachary Hartman and Andrea Amalfitano

15 Alphaviral-Based Strategies for the Immunotherapy of Cancer ..................... 203 Edward L. Nelson and Jonathan Smith

16 DNA Vaccines .................................................................................................. 225 Michael Bereta and Howard L. Kaufman

17 Whole-Cell Vaccines ........................................................................................ 249 Timothy M. Clay, Paul J. Mosca, H. Kim Lyerly, and Michael A. Morse

18 Gene-Modified Tumor-Cell Vaccines ............................................................. 253 Leisha A. Emens and Elizabeth M. Jaffee

19 Hapten-Modified Tumor Vaccines .................................................................. 275 David Berd

20 Chaperone Proteins/Heat Shock Proteins As Anticancer Vaccines ................ 297 Michael W. Graner and Emmanuel Katsanis

21 Dendritic Cell Vaccines .................................................................................... 317 Madhav V. Dhodapkar

22 Exosomes for Immunotherapy of Cancer ........................................................ 331 Nathalie Chaput, N. E. C. Schartz, Fabrice Andre,

and Laurence Zitvogel

23 Immunocytokines for Cancer Immunotherapy ................................................ 341 Paul M. Sondel and Steven D. Gillies

24 T-Cell Adoptive Immunotherapy ..................................................................... 359 Gregory E. Plautz, Peter A. Cohen, David E. Weng, and Suyu Shu

PART III: TUMOR-SPECIFIC VACCINE DEVELOPMENT

25 Melanoma Vaccines ......................................................................................... 379 Jeffrey Weber

26 Allogenic Melanoma Lysate Vaccines ............................................................ 397 Malcolm S. Mitchell

27 Renal Cancer Vaccines ..................................................................................... 415 Hyung L. Kim, Barbara J. Gitlitz, and Robert A. Figlin

28 Vaccines for Hematological Malignancies ...................................................... 425 Qing Yi

29 Vaccines for the Immunotherapy of Prostate Cancer ...................................... 451 Boris Minev and Michael L. Salgaller

30 Vaccine Therapy for Breast and Ovarian Cancers .......................................... 465 Susan E. Smith and Alison T. Stopeck

31 Vaccine Therapy for Gastrointestinal Cancers ................................................ 491 John L. Marshall

Contents ix

32 Vaccines for Lung Cancer ................................................................................ 505 Michael A. Morse, Jennifer Garst, and Eric Toloza

33 Vaccines for Other Tumors .............................................................................. 513 Michael A. Morse

PART IV: CLINICAL TRIALS AND IMMUNE ANALYSES

34 Clinical Trial Designs for Therapeutic Vaccine Studies ................................. 519 Richard Simon

35 Analysis of Cellular Immune Responses in Cancer Vaccine Trials ............... 527 Timothy M. Clay, Michael A. Morse, Paul J. Mosca, Amy Hobeika,

Donna Niedzwiecki, and H. Kim Lyerly

36 Analysis of Humoral Immune Responses in Vaccine Trials ........................... 543 Rajasekharan Somasundaram, Tianqian Zhang,

and Dorothee Herlyn

37 Regulatory Issues Affecting Tumor Vaccines ................................................. 563 Mark O. Thornton, Alexandra S. Worobec, Keith Wonnacott,

and Raj K. Puri

Index ........................................................................................................................... 577

CONTRIBUTORS

ANDREA AMALFITANO, DO, PhD· Departments of Pediatrics, Molecular Genetics and Microbiology, and Pathology, Duke University Medical Center, Durham, NC

FA BRICE ANDRE, MD· Department of Clinical Biology, Institut Gustave Roussy (IGR), Villejuif, France

PHILIP M. ARLEN, MD • Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD

JORY R. BALDRIDGE, PhD • Corixa Corporation, Hamilton, MT

DAVID BERD, MD • Division of Medical Oncology, Department of Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA

MICHAEL BERETA, PhD • Department of Surgery and Pathology, Columbia University, New York, NY

CARMEN M. BERGER, MD· Division of Dermatology, University of Washington, Seattle, WA

MALAYA BHATTACHARYA-CHATTERJEE, PhD· Department of Internal Medicine and the Barrett Cancer Center, University of Cincinnati, Cincinnati, OH

GERARD C. BLOBE, MD, PhD • Departments of Medicine and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC

SUNIL K. CHATTERJEE, PhD· Department of Internal Medicine and the Barrett Cancer Center, University of Cincinnati, Cincinnati, OH

NATHALIE CHAPUT, PhannD • Department of Clinical Biology, Institut Gustave Roussy (IGR), Villejuif, France

TIMOTHY M. CLAY, PhD· Department of Surgery, Duke University Medical Center, Durham, NC

PETER A. COHEN, MD· Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, OH

DIANE M. DA SILVA, PhD· Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL

MARY L. DISIS, MD • Division of Oncology, University of Washington, Seattle, WA

MADHAV v. DHODAPKAR, MD· Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, and Hematology Service, Memorial Sloan Kettering Cancer Center, New York, NY

GRETCHEN L. EIBEN, BS· Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL

LEISHA A. EMENS, MD, PhD • Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD

STEVEN C. FAUSCH, BS • Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL

xiii

xiv Contributors

ROBERT A. FIGLIN, MD • Departments of Medicine and Urology, University of California, Los Angeles, CA

JOHN FIKES, PhD • Epimmune Inc., San Diego, CA

KENNETH A. FOON, MD • Abgenix Inc., Fremont, CA

DMITRY GABRILOVICH, MD, PhD • H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL

JENNIFER GARST, MD • Department of Medicine, Duke University Medical Center, Durham, NC

JOHN GATHURU, PhD· Laboratory of Tumor Vaccinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

STEVEN D. GILLIES, PhD· EMD Lexigen Research Center Corporation, Bedford, MA

BARBARA J. GITLI1Z, MD· Department of Medicine, University of California, Los Angeles, CA

MICHAEL W. GRANER, PhD· Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, AZ

JAMES L. GULLEY, MD, PhD· Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD

ZACHARY HARTMAN, BA • Departments of Pediatrics and Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC

DOROTHEE HERL YN, DVM • The Wistar Institute, University of Pennsylvania, Philadelphia, PA

AMy HOBEIKA, PhD • Department of Surgery, Duke University Medical Center, Durham, NC

ELIZABETH M. JAFFEE, MD • Departments of Oncology, Pathology and Immunology, The Johns Hopkins University School of Medicine, Baltimore, MD

EMMANUEL KATSANIS, MD· Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, AZ

W. MARTIN KAST, PhD· Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL

HOWARD L. KAUFMAN, MD • Department of Surgery and Pathology, Columbia University, New York, NY

HYUNG L. KIM, MD • Department of Urology, University of California, Los Angeles, CA

KEITH L. KNUTSON, PhD • Division of Oncology, University of Washington, Seattle, WA

AMANDA M. KRIER, BS • Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL

CAROLINE LE POOLE, PhD • Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL

PHILIP O. LIVINGSTON, MD • Laboratory of Tumor Vaccinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

H. KIM LYERLY, MD· Departments of Surgery, Immunology, Pathology, Duke University Medical Center, Durham, NC

JOHN L. MARSHALL, MD • Developmental Therapeutics and GI Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC

Contributors

BORIS MINEV, MD • UCSD Comprehensive Cancer Center, University of California, San Diego, CA

MALCOLM S. MITCHELL, MD· Barbara Ann Karmanos Cancer Institute, The Detroit Medical Center, Wayne State University, Detroit, MI

MICHAEL A. MORSE, MD· Department of Medicine, Duke University Medical Center, Durham, NC

PAUL J. MOSCA, MD, PhD • Department of Surgery, Duke University Medical Center, Durham, NC

SALLY P. MOSSMAN, PhD· Corixa Corporation, Seattle, WA

EDWARD L. NELSON, MD· Division of Hematology/Oncology and Department of Molecular Biology and Biochemistry, University of California, Irvine, CA

DONNA NIEDZWIECKI, PhD • Department of Bioinformatics and Bioinformatics, Duke University Medical Center, Durham, NC

MICHAEL I. NISHIMURA, PhD· Department of Surgical Oncology, The University of Chicago Medical Center, Chicago, Maywood, IL

MICHAEL J. PALMOWSKI, DPHIL· Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

MEGAN E. PAPINEAU, BS • Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL

VLADIMIR PISAREV, MD, PhD • Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE

GREGORY E. PLAUTZ, MD • Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, OH

RAJ K. PURl, MD, PhD • Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation & Research, Food and Drug Administration, Rockville, MD

xv

GOVIND RAGUPATHI, PhD· Laboratory of Tumor Vaccinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

PAUL F. ROBBINS, PhD· Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD

MICHAEL L. SALGALLER, PhD • Toucan Capital Corp., Bethesda, MD

LUPE G. SALAZAR, MD· Division of Oncology, University of Washington, Seattle, WA

N. E. C. SCHARTZ, MD· Department of Clinical Biology, Institut Gustave Roussy (IGR), Villejulf, France; Department of Dermatology 2, AP-HP Hopital Saint-Louis, Paris, France

KATHY SCHIFFMAN, PA-C· Division of Oncology, University of Washington, Seattle, WA

JEFFREY SCHLOM, PhD· Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD

SUYU SHU, PhD • Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, OH

RICHARD SIMON, DSc • Biometric Research Branch, National Cancer Institute, Rockville, MD

CAROLINE SMITH, MD • Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

xvi Contributors

JONATHAN SMITH, PhD· AlphaVax, Research Triangle Park, NC

SUSAN E. SMITH, MD • Arizona Cancer Center, University of Arizona, Tucson, AZ

RAJASEKHARAN SOMASUNDARAM, PhD • The Wistar Institute, University of Pennsylvania, Philadelphia, PA

PAUL M. SONDEL, MD, PhD· Comprehensive Cancer Center, University of Wisconsin, Madison, WI

ALISON T. STOPECK, MD • Arizona Cancer Center, University of Arizona, Tucson, AZ

MARK O. THORNTON, MD, MPH, PhD· Division of Therapeutic Biologic Oncology Products, Center for Drug Evaluation and Review, Food and Drug Administration, Rockville, MD

ERIC TOLOZA, MD, PhD • Department of Surgery, Duke University Medical Center, Durham, NC

JEFFREY WEBER, MD, PhD • USC/Norris Cancer Center, University of Southern California, Los Angeles, CA

DAVID E. WENG, MD, PhD • Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, OH

KEITH WONNACOTT, PhD • Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation & Research, Food and Drug Administration, Rockville, MD

ALEXANDRA S. WOROBEC, MD • Division of Clinical Trial Design and Analysis, Center for Biologics Evaluation & Research, Food and Drug Administration, Rockville, MD

JIANGCHUN Xu, MD, PhD • Corixa Corporation, Seattle, WA

QING YI, MD, PhD • Myeloma Institute for Research and Therapy and Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, AR

TIANQIAN ZHANG, PhD· The Wistar Institute, University of Pennsylvania, Philadelphia, PA

SUSAN HAND ZIMMERMANN, PhD· Corixa Corporation, Seattle, WA

LAURENCE ZITVOGEL, MD, PhD • Department of Clinical Biology, Institut Gustave Roussy (IGR), Villejuif, France

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