Cancer immunotherapy – broader considerations

Abstract

Cancer Vaccines and Immunotherapyedited by Peter L. Stern, Peter L.C. Beverley and Miles W. CarrollCambridge University Press, 2000. £55.00 hdbk (x + 286 pages) ISBN 0 521 62263 8Writing a book on cancer vaccines and immunotherapy must be an extremely daunting task, considering the range of topics available and the vast number of specific reviews appearing continually in the literature. This is a clearly presented and considered book on cancer vaccines, which encapsulates the past decade of discovery of new tumor antigens (Ags), vector-delivery systems and functions of Ag-presenting cells. It meets successfully a need to summarize past developments in the immunotherapeutic treatment of a range of malignant diseases that each pose their own specific problems. In this sense, Cancer Vaccines and Immunotherapy is a good introduction to established strategies of cancer vaccination for clinical oncologists and immunologists.Strengths of the book include the in-depth, analytical chapters on the immunotherapy of bladder cancer, cervical cancer and Epstein–Barr-virus-associated cancers. The chapters that concentrate on MUC-1 and carcinoembryonic antigen (CEA) as targets for breast and colon cancer, respectively, are more focused and, therefore, less universally informative – a greater discussion of alternative targets and approaches in these major, problematical diseases would have been beneficial. An unfortunate omission is the use of hematopoietic-cell transplantation in leukemia, because this is one of the clearest examples of the power of the immune system to eradicate cancer.The scope of this volume is narrow in that it does not cover all types of immunotherapy. For example, the chapter that discusses melanoma-specific cytotoxic T lymphocyte (CTL) vaccines did not extend much upon the informative, preceding chapter on novel Ags characterized by serological identification of recombinantly expressed genes (SEREX). Given the high level of activity of immunologists in research into melanoma during the past 20 years, perhaps a broader view of the immunotherapy of melanoma, including adoptive immunotherapy and other cellular-therapy approaches would have been more balanced. Gene-therapy approaches to modify tumor cells by the expression of cytokines and costimulatory molecules were also not discussed in any detail, despite evidence of some early clinical and experimental promise using these approaches. The focus by researchers on characterizing new tumor Ags recognized by CTLs, rather than developing rapid and reliable clinical screens for the most relevant tumor Ags, is reflected by the weighting these topics receive in the book. Concerning the delivery of tumor Ags, the chapter covering the use of poxviruses as vectors is excellent and well-pitched, although it might have benefited from some historical perspective, such as that presented in the following chapter. There are two successive chapters on the use of these vectors in the treatment of cervical cancer, but the reader might prefer to have been informed in greater depth about alternative, promising strategies, such as the use of virus-like particles and polytope vaccines.The editorial overviews at the start and conclusion of this book effectively introduce and draw together, respectively, the topics at hand. However, despite major advances in our understanding of adaptive immunity and dendritic cells (DCs), consistent and durable responses to cancer vaccines remain elusive, and active immunotherapy is not an established treatment modality yet. Given that the editors favor vaccines operating through the function of DCs, it is perplexing that more attention was not focused on the biology of these cells and the various methods by which they can be manipulated. In particular, the concept that pattern-recognition receptors and ‘danger’ signals link innate to adaptive immunity is barely considered. More-theoretical aspects, such as whether efficient immune reactions can be generated against virus-noninfected tumors are also largely ignored. In this sense, the book suffers from an imbalance. Broader, important and often, more-novel themes of cancer immunotherapy, such as Matzinger's ‘danger’ hypothesis; the role of innate immunity; the role of costimulators, including cytokines and surface receptors that promote effector function; immunosuppression mediated by the tumor; and immune regulatory T cells and tolerance are not considered (even in the chapter on recent developments). In addition, many chapters lack effective, educational or interesting figures to illustrate the key theoretical concepts or clinically impressive data.In summary, this book provides a good overview of the clinical focus of cancer immunotherapy over the past decade and an entry point for those wanting to understand how the discovery of new tumor Ags and vectors has shaped current thinking about CTL-based vaccines. Mounting evidence suggests that we must move towards applying the safest and most effective CTL vaccines for the treatment of appropriate patients with minimal residual tumor burden. It remains feasible to design vaccines that are based on rational immunological principles. Nevertheless, much needs to be learned about the signals elicited by transformed cells, and we must determine how and why certain Ags can variously be stimulatory or tolerogenic for the immune response to cancer.