Cell Therapy Stem Cell Transplantation, Gene Therapy, and Cellular Immunotherapy,

BOOK REVIEW Cell Therapy: Stem Cell Transplantation, Gene Therapy, and Cellular Immunotherapy, edited by George Mortsyn and William Sheridan (New York: Cambridge Univer- sity Press, 1996).

This 617-page book is one volume in the series Cancer: Clinical Science in Practice, edited by Professor Karol Sikora from the Department of Clinical Oncology of Hammersmith Hospital in London. Although intended for a diverse, but sophisticated, audience in the fields of clinical oncology and bone marrow trans- plantation, immunology, molecular and cellular biology, virology, and biotech- nology, the reader needs only basic knowledge of these areas to access the wealth of information provided in this volume. It is a collection of concise reviews on various associated topics aimed at defining the need, potential, and reality of cancer immunotherapy, the indications for high-dose chemotherapy, and ap- proaches to stem cell transplantation. The editors and authors lead the reader through a maze of cytokines and stem cells, gene therapy, basic concepts of high- dose chemotherapy and stem cell transplantation, as well as newer adoptive cell therapy approaches. The editors, George Morstyn and William Sheridan, are acknowledged pioneers in the use of cytokines and stem cell transplantation, having been involved in early efforts in both the US and Australia and in the context of their leading roles at Amgen. Hence, the book draws on a wide variety of sources, available by virtue of the editors' experience, with many of the sources recognized experts in their own right. The text is divided into three sections. The first, "Aspects of Hemopoiesis and the Immune System Important for Cell Therapy," is a well-written review of hemopoiesis, bone marrow microenvironment, and marrow reconstitution. Dif- ferent methods of measuring and enumerating the quantity and quality of bone marrow constituents and hematopoietic precursor cells and their own inherent difficulties are reviewed, giving the reader adequate information to formulate a vision of this complex field and the direction in which it is moving without rendering it cumbersome in detail. Procedures and cellular subsets involved in antigen-specific and nonspecific cell therapy for antitumor immunotherapy are described and methods for adoptive transfer of immune cells are introduced. An ambitious chapter by Shimon Slavin reviews the range of potential effector

JOURNAL OF URBAN HEALTH: BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE VOLUME 75, NUMBER 4, DECEMBER 1998 922 Q 1998 THE NEW YORK ACADEMY OF MEDICINE BOOK REVIEW 923 cells usable for transplantation and immunotherapeutic purposes. This chapter tends to focus a bit too heavily on the author's own achievements in the field, at the expense of more widely accepted principles of immunotherapy, and would have benefited from additional development of the topic of dendritic cell use, the importance of the T-cell costimulatory pathway, and the requirement for development of long-term immunologic memory. The author, however, does present a unique perspective on the use of macrophages, as well as natural killer cells, in immunotherapy. The second section, "Hemopoietic Cell Therapy," reviews the scientific princi- ples of defining and utilizing stem cell populations, the technology of progenitor cell collection, and potential clinical applications. A brief overview of a broad subject is presented in the first chapter, ranging from ex vivo hemopoietic expan- sion and CD34+ selection, to the collection of other cellular compartments, such as tumor-infiltrating lymphocytes and lymphocyte-activated killer cells. Many, if not all, of the concepts in this chapter are developed further elsewhere in the book to provide needed detail. Difficulties inherent in human progenitor cell assays are outlined, stressing the need for the standardization of techniques and reporting within and between laboratories. The reader, however, will need to seek additional sources for technical details of these assays. The chapter on flow cytometry is expertly written, and attractive color plates assist in interpretation of the descriptions of the technique. The cartoons and diagrams included in the chapter on gene therapy are also quite beneficial, and adequate information is provided to understand the clinical relevance in the chapters that follow. The chapter on gene therapy is particularly well written, although already dated given the rapid evolution of the field. A concise overview of retroviral and adeno- associated virus transduction is provided, although the controversy surrounding use of adeno-associated virus for stable transduction is only briefly discussed. Additional information regarding emerging retroviral transduction systems based on vesicular stomatitis virus pseudotyped vectors and/or vectors derived from human immunodeficiency virus would have rounded out an otherwise excellent chapter by Bodine on gene therapy. The next portion of this section emphasizes hematopoietic progenitor cell sources, selection, collection, and preparation. Bone marrow, peripheral blood progenitor, and cord blood sources are all considered, and strategies for and early efforts in ex vivo expansion and reinfusion are discussed. Mobilization of peripheral blood progenitor cells with chemotherapy alone, growth factors alone, or in combination is reviewed. Advantages of each approach, as well as the optimal timing of leukopheretic harvests, are outlined. Tables and graphs summa-