Experimental and applied immunotherapy, 1st edn

Abstract

Experimental and applied immunotherapy, 1st edn . Medin, Jeffrey & Fowler, Daniel , eds. Published by Humana Press , New York, NY, USA , 2011 . 442 pp, price £135, ISBN: 978-1-60761-979-6 Experimental and Applied Immunotherapy is a highly informative compendium of essays with a heavy focus on cancer immunotherapy. The book title is overly general and ignores the fact that clinicians have been practising immunotherapy to treat allergic disease for many years. Nonetheless, the essays are excellent and present the state of the art of many emerging and established immunotherapies for cancer. Over 150 000 deaths in Britain each year result from cancer, a figure that continues to increase, year on year. While there has been a recent flurry of novel cancer therapeutics, some of those approved by the FDA have led to a prolongation of median survival of the order of only a few days. Consequently, the pressing need for new treatments is clear. In presenting immunotherapy as one such approach, the preface by June sets the scene. The challenge of commercializing cell therapy is rightly presented as a key obstacle, leading to delays in clinical translation. By contrast, the ever-strengthening clinical impact and commercial position of monoclonal antibody therapy is described by Rader, who points out that these agents comprised the top three cancer drugs based upon global sales in 2008. Approximately one third of the 21 chapters are devoted to T-cells. However, a discrete chapter describing the development and application of immunotherapy using tumour-infiltrating lymphocytes (TIL) would have been a welcome addition. Use of gene transfer to direct T-cell specificity is appropriately discussed as a device to generate therapeutic products rapidly ex vivo. Technologies under study include the delivery of ectopic T-cell receptor dimers or alternatively the use of novel fusion receptors, known as chimeric antigen receptors (CAR). The latter engage native antigen, thereby bypassing the need for HLA expression or restriction. Pre-clinical and clinical testing of both approaches is described although reference to ongoing UK clinical trials is disappointingly omitted. Furthermore, recent fatal toxic events attributed to CAR-based clinical immunotherapy are referred to, although not dissected in great detail. Separate chapters describe other relevant cell types, including B-cells, regulatory T-cells, natural killer cells, mesenchymal stromal cells and myeloid inhibitory cell types. Unfortunately however, gamma delta T-cells were not the subject of an individual chapter. This small T-cell population is attracting much interest owing to their role in tumour immunosurveillance. Furthermore, the primary circulating human gamma delta T-cell population can be activated and expanded ex vivo with the use of clinically available nitrogen-containing bisphosphonates, providing exciting opportunities for adoptive T-cell immunotherapy. Immunization approaches are considered by several authors. The development of sipuleucel-T for prostate cancer is described in the chapter on dendritic cell vaccines. This patient specific cellular vaccine is a prototypic cell therapy, now licensed by the FDA having achieved a prolongation of median survival of 4.1 months in a recent phase III trial. Cytokine therapy is also covered, with appropriate emphasis on the development of genetic/targeted delivery systems to address pharmacokinetic challenges and toxicity. The final chapters present a number of combinatorial approaches, probably reflecting where the future really lies. In summary, despite the somewhat sub-optimal graphics, I can recommend this excellent collection of succinct essays that span the breadth of ongoing research in cancer immunotherapy. There are no competing interests to declare.