Molecular chaperones as inducers of tumour immunity

Introduction Tumour antigens can be broadly classified into four categories: (i) those that are expressed in larger quantities in tumours than their normal counterparts (e.g., tumour-associated carbohydrate antigens) [1], (ii) onco-fetal antigens (e.g., carcinoembryonic antigen) [2], (iii) differentiation antigens (e.g., melanoma differentiation antigen) [3, 4] and (iv) tumour-specific antigens. Tumour antigens in the first three categories could serve as useful markers for diagnostic and prognostic purposes. Although some of these antigens are being used in immunotherapy, none can be called tumour-specific in a true sense. Only the last group includes antigens that are truly specific for tumour cells, in that they contain tumour-specific mutations that are unique for individual tumours such as the tumour-specific point mutation that is found in cyclin-dependent kinase-4. Such a mutation gives rise to a novel antigenic epitope which can be recognised by cytotoxic T lymphocytes (CTLs) [5]. However, for these antigens to be of any value as therapeutic agents, they must be detected in and epitopes isolated from a large range of cancers, and this makes the general use of these antigens difficult. In the past two decades, evidence has accumulated to support the concept that molecular chaperones or heat shock proteins can be used as a potent source of cancer vaccines [6, 7]. Molecular chaperones, particularly those derived from the Hsp70 and Hsp90 families, are now being tested in the clinical arena for therapeutic efficacy against a range of cancers (Table 18.1).