Cancer Immunotherapy Via the Residual Repertoire

The available postthymic residual repertoire specific for self antigens, is, in part, comprised of clones that evaded negative selection, either because of their low affinity for antigen, or because their complementary self-determinant failed to gain access to the MHC to permit tolerance induction. This repertoire may serve as a convenient source of cells for generating an anticancer response, based on the contention that most tumor-associated antigens are actually highly expressed normal self-antigens. Most often, these clones will be directed against subdominant or cryptic determinants, and therefore attempts have been made to alter their target determinants to convert them into more effective immunogens, able to induce proinflammatory Th1 responses (29). Other approaches include the enhancement of costimulatory effects (30,31) and the neutralization of inhibitory elements such as CTLA-4 (32). It is evident that the interests of the autoimmunologist and the tumor immunologist merge in seeking ways to provide immunotherapy against this set of chronic diseases. The fortuitous escape by certain clones from destruction, provides tools for the clever cancer immunothera-pist providing she succeeds in evading the clutches of the regulators.

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