Blood Malignancies and Treatment

Biography

Biography: Shimon Slavin

Abstract

Immunotherapy represents the treatment of choice against chemo-radioresistant malignant cells and cancer stem cells that are a prioi resistant to anti-cancer modalities. The documented therapeutic effects of donor lymphocyte infusion (DLI) following maximally tolerated myeloablative chemo radiotherapy following allogeneic stem cell transplantation (SCT) suggests that cell-mediated immunotherapy may represent the treatment of choice for elimination of otherwise resistant malignant cells. Accordingly, we have developed a new approach for induction of graft-vs-malignancy (GVM) effects by intentionally mismatched IL-2 activated killers (IMAK) while avoiding GVHD following conventional chemotherapy or haploidentical SCT using reduced intensity conditioning (RIC) followed by post transplant elimination of host and donor’s alloreactive T cells for prevention of rejection and GVHD. Long-term GVM effect was induced post-SCT by IL-2 activated donor NK cells prepared by negative selection of CD3+ T cells or positive selection of CD56+ NK cells. Mismatched NK cells induced most effective GVM while avoiding GVHD in patients with resistant relapsed Leukemia. Short-term GVM effects with no prior SCT was accomplished by haploidentical or unrelated IMAK activated in vitro and in vivo following infusion with low dose IL-2 for 5 days. More effective and more selective GVM effects against residual cancer cells could be accomplished using monoclonal or bispecific antibodies bound to Fc receptors on killer cells targeting killer cells against antigens over-expressed on malignant cells (e.g. Rituximab or Pinatumomab against B cell malignancies). Using IMAK against MRD following conventional chemotherapy or SCT can result in cure of otherwise resistant hematological malignancies while avoiding GVHD.