Comparative Evaluation of Kit-M (GM-CSF and PGE-1) and Kit-I (GM-CSF and Picibanil) for the Generation of DCs/DCleus and Their Impact on Subsequent Antileukemic Immune Cell Activation Ex Vivo.

Background/Objectives: Novel (immune) therapies are needed to stabilize the disease or achieve remissions in AML. We already demonstrated that DCleus can be generated ex vivo from AML patients' blasts in WB using approved drugs (GM-CSF and PGE-1 (Kit-M) or GM-CSF and Picibanil (OK-432), Kit-I). The generated DCleus induce antileukemia-directed immune cells of the adaptive and innate immune system, enabling leukemia-specific immune activation after MLC. Methods: We compared the effects of Kit-I vs. Kit-M by quantifying (1) their potential to produce DCs/DCleus from WB samples from 6 healthy individuals and 28 AML patients' WB in different stages of the disease and (2) the activation of adaptive and innate leukemia-specific IFNγ-producing or degranulating antileukemic cells after MLC with and without Kit-I/Kit-M-pretreated WB. Furthermore, we correlated the obtained results with the achieved improved cells' antileukemic functionality and patients' clinical data. Results: In AML samples we found significantly higher frequencies of (mature) DCleus generable without induction of blast proliferation in Kit-M as well as (although less pronounced) in Kit-I-treated vs. untreated samples, a significant increase in the frequency of (leukemia- specific) immunoreactive cells, and improved blast cytotoxicity after MLC with Kit-M and with Kit-I-treated vs. untreated samples (potentially with higher induction of CD4 and CIK IFNγ + cells in Kit-I-pretreated samples). These data might suggest that both Kits work via different pathways. Conclusions: We show that Kit-M and Kit-I produce DCs/DCleus and subsequently enhance (potentially via a different mode of action) antileukemic immune cell activation after MLC. Our findings point to a possibility to enhance antileukemic treatment in vivo by combining agents or identifying criteria for selecting an appropriate agent (combination) for the respective patient in the course of a personalized treatment strategy.