BCG’s Mechanism of Action – Increasing our Understanding

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Abstract
BCG immunotherapy against superficial bladder carcinoma recurrences is regarded as the most successful to date. However, the mode of action has not yet been fully explained. In this field, several European groups have recently significantly contributed by adding more details to the complex picture of the immunological processes of BCG effector mechanisms. BCG inflammation obviously differs from non-specific inflammation by its quality and subclinical duration. Infiltration of immunocompetent cells into the bladder wall with secretion of cytokines into the urine has been characterized. Specific humoral responses of patients towards mycobacterial antigens have been determined. These data clearly present a large body of evidence that the inflammatory reaction induced by BCG correlates with the anti-tumour response. In vitro models of cytotoxic effector cells have shown interesting and selective effector mechanisms induced by BCG. Animal models have proven valuable in supporting ex vivo and in vitro data and in clarifying new aspects of the application of BCG in vivo. Future research efforts will certainly add understanding to the immediate and long-term humoral and cellular responses. All our investigations intend to define clearly surrogate parameters for efficacy and side-effects, to increase therapeutic efficacy further and to decrease side-effects associated with this therapy. Only the collaborative efforts of several groups will be able to achieve a highly effective immunotherapeutic regimen against bladder carcinoma.

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