Current problems in the development of specific immunotherapeutic approaches to cancer

Over the past decade there has been a widespread resurgence of interest in the concept of cancer immunotherapy and the design of new cancer vaccines. The discovery of tumour specific and tumour associated antigens has resulted in a large number of targets that are currently being developed as potential clinical products. These are comprehensively reviewed by Jäger et al.¹

Although the identification of tumour antigen epitopes by cytotoxic T lymphocytes (CTL) is certainly an elegant and logical approach, there is a disturbing lack of correlation between CTL activity to these epitopes and clinical response.² Moreover, it seems that there is a distinctive lack of help for a second signal in many reductionistic approaches because responses are often seen only after the addition of interleukin 2 (IL-2).³

In addition to specific immune responses, it may be that an appropriate innate immune response is as important or more important for cancer immunotherapy to be effective. Indeed, there are many reports of non-specific treatments, such as interlesional BCG or systemic cytokines such as interferon and IL-2, having singular activity in malignant melanoma and renal cell cancer.⁴ The role of non-specific immunomodulators appears …