Induction of anti-leukemic responses using cellular immunotherapy (TUM2P.921)

Abstract

Abstract Previous work has shown that blood cancers can be treated through stimulation of the cancer patient’s immune system. In initial studies, it was observed that 14/26 patients with refractory hematological malignancies responded (9 major) to the infusion of large numbers (1 -2 x 108 CD3+ cells/kg) of haploidentical white blood cells following low levels of total body irradiation (100cGy). A cytokine storm quickly developed with a median time of 14 hours and resulted in high fevers that were allowed to persist for 48 hours, if possible, and then controlled with corticosteroids if needed. However the potential role of anti-leukemic effector cells in these responses was not determined. Three patients have been enrolled into a re-opened cellular immunotherapy clinical trial in which haploidentical white blood cells are infused with no prior chemotherapy or radiation. Blood samples were obtained from the recipient approximately 1, 24, 48, 72 and 168 hours after infusion and analyzed for the persistence and activity of donor/recipient cells as well as levels of cytokines and other factors in the plasma. Thus far, the results demonstrate elimination of donor cells by day 7, rapid upregulation of PD-1 ligands on leukemic cells and prolonged plasma levels of IL-10. Evaluation of the trends obtained with increased number of patients enrolled in the clinical trials will provide insights into new approaches to enhance the anti-leukemic responses in these patients.