Reconstructing an Anti-Tumor Immune Repertoire for Targeted AML Therapy.

Selectively shaping the T cell repertoire in hemopoietic stem cell transplantation and leukemia immunotherapy towards specific recognition and elimination of malignant and virus-infected cells represents a new therapeutic concept. This concept takes advantage of selectively tolerizing or depleting graft versus host disease (GvHD)-mediating T lymphocytes, while preserving or selecting cytotoxic T cell responses specific for malignant and viral disease. Two specific strategies have been extensively explored in preclinical models for this particular purpose. One strategy is to equip recipient-derived T lymphocytes with "off the shelve" available T cell antigen receptors (TCRs) specific for leukemia-associated as well as human cytomegalovirus (hCMV)- specific antigenic epitopes in order to tackle leukemic relapse and hCMV infection. This strategy is obviously as attractive in immunotherapy of malignant disease by transferring specificity and affinity of TCRs for broadspectrum tumor- and leukemia-associated antigens into T lymphocytes of patients and thus breaking their state of cancer- and leukemia-specific T cell tolerance. Another strategy is to selectively deplete the donor stem cell graft of GvHD-mediating alloreactive T lymphocytes while preserving the integrity of a leukemia- and virus-reactive T cell repertoire within the stem cell inoculum. As these strategies have been successfully developed at the preclinical level, the opportunity of transferring them into clinical application represents a possible current challenge and endeavor. Keywords: Cytotoxic T lymphocytes; T cell antigen receptor; allogeneic hemopoietic stem cell transplantation; acute myeloid leukemia [ABSTRACT FROM AUTHOR]