Therapeutic vaccination for cancer: The potential value of mycobacterial products

Attempts to treat cancer by various forms of immunotherapy were first made over a century ago. Initial attempts were based on the empirical use of bacterial toxins and probably acted by inducing tumour necrosis factor, together with type 2 cytokines. Following the discovery of tumour-specific antigens in 1953, many attempts were made to stimulate immune defences non-specifically, and the use of Bacille Calmette-Guerin (BCG) figured prominently in these attempts but with very variable responses. In recent years, advances in knowledge of the molecular and cellular basis of both cancer and the immune system have led to more rational approaches. In particular, the finding that there are several quite distinct cytokine-mediated types of immune reactivity has led to attempts to selectively enhance the reactions most effective in destroying cancer cells and down-regulating responses which may antagonise the effective reactions. Although type 2 cytokine mediated responses may be effective in some situations, there is increasing evidence that effective antitumour immune responses are likely to be mediated by type 1 cytokines. While the commonly used living BCG vaccine is a powerful adjuvant it is able, depending on prior environmental sensitisation, to evoke either Th1 or Th2 responses and may thus be a two-edged sword in cancer immunotherapy. Recently investigations indicate that another mycobacterial preparation, heat-killed Mycobacterium vaccae, is a more reliable Th1 adjuvant and preliminary clinical trials indicate beneficial effects in melanoma, and cancer of the prostate and lung. More extensive controlled studies are currently being conducted to confirm these findings.