Antigen-specific cellular immunotherapy of leukemia

Advances in cellular and molecular immunology have led to the characterization of leukemia-specific T-cell antigens and to the development of strategies for effective augmentation of T-cell immunity in leukemia patients. While several leukemia-related antigens have been identified, this review focuses on the Wilms' tumor 1 (WT1) antigen and the proteinase 3 (Pr3) antigen that are overexpressed in leukemic cells and are already being used in the clinical setting. Moreover, WT1 is also overexpressed in a vast number of nonhematological solid tumors, thereby expanding its use as a promising target for cancer vaccines. Examples of spontaneous immune responses against WT1 and Pr3 in leukemia patients are presented and the potential of WT1 and Pr3 for adoptive T-cell immunotherapy of leukemia is discussed. We also elaborate on the use of professional antigen-presenting cells loaded with mRNA encoding WT1 exploiting the advantage of broad HLA coverage for therapeutic vaccination purposes. Finally, the summarized data underscore the potential of WT1 for the manipulation of T-cell immunity in leukemia and in cancer in general, that will likely pave the way for the development of more effective and generic cancer vaccines.