Book Review: Cancer Vaccines and Immunotherapy
Authors: Karen McAdam
Journal: Journal of the Royal Society of Medicine (2001)

An increasing ability to identify tumour antigens, coupled with advances in immunization, has generated new enthusiasm for cancer vaccination strategies. Cancer Vaccines and Immunotherapy describes the underlying mechanisms and the therapeutic potential of this approach.

The short and lucid introduction is essential for an understanding of what follows: it deals with immunosurveillance and how it may be affected in cancer, with immune-mediated elimination of allogeneic tumours in animal models, with the successful treatment of Epstein—Barr virus related lymphoma in renal transplant patients by infusion of immune T cells, and with the way the immune system recognizes and processes tumour antigens, what induces self-tolerance, and which additional molecules are required for an effective immune response. A chapter on pox viruses, one of the principal delivery vehicles for tumour vaccines, serves as useful background to the discussion of clinical trials.

The hope, of course, is that vaccination will improve on the results of conventional therapies, especially for common tumours such as breast cancer. In this respect there has been much interest in the MUC1 gene, which encodes for an epithelial mucin overexpressed in malignant breast cells and associated with an altered pattern of glycosylation (though the relevance of this to cell behaviour is unknown). MUC1 can also act as a ligand for the adhesion molecule ICAM-1 and enhances antigen presentation to T cells, possibly via interaction with a lectin molecule. A multitude of antibodies have been raised to MUC1 and some are being used in clinical trials of immunotherapy for breast and ovarian cancer. Early results are promising and phase III studies are underway.

One of the key chapters deals with an approach termed SEREX (serological analysis of tumour antigens by recombinant cDNA expression cloning). This involves the construction of cDNA expression libraries from fresh tumour specimens and the selection of clones that elicit high-titre IgG antibody responses. Some of the advantages of this technique are that tumour lines do not have to be established, identified genes are expressed in vivo and multiple antigens can be identified with one screening course and sequenced immediately. By 1998 there were over nine hundred entries on the SEREX database. This technique may allow mapping of the antigenic profile of individual tumours, identification of the antigens that elicit an immune response in cancer patients, and the development of polyvalent vaccines.

Although techniques of this kind offer hope that novel treatments will soon emerge, the overview in Cancer Vaccines and Immunotherapy sounds some notes of caution. Of the antigens identified by SEREX few have reached the stage of preclinical trial, so the full limitations of the method have probably yet to emerge. Of the various delivery mechanisms for vaccines, all have advantages and disadvantages. And the remaining challenge is to optimize the design of clinical trials to ensure that vaccines are not only immunogenic and effective but also safe. This requires development of better tools for assessing immunological and clinical aspects. The choice of malignant target and stage of disease is also important.

Despite all the scientific advances there is still no certainty that cancer vaccines will work efficiently. The vaccine for which the evidence is strongest, BCG for bladder cancer, is based on the old non-specific approach. But there is sufficient evidence in this valuable survey to warrant a degree of optimism.