UMBILICAL CORD BLOOD (UCB) AND BONE MARROW (BM) AS A SOURCE OF NATURAL KILLERS (NK) FOR KIR-ALLOREACTIVE ADOPTIVE IMMUNOTHERAPY (KIR-AI)

Abstract

Objective: NK are innate lymphoid cells with the ability to rapidly recognize and exhibit cytotoxicity toward tumor and virus infected cells in HLA-independent manner without prior activation. KIR-AI is the next promising step after KIR-alloreactive NMAC alloBM transplantation (not only in hematology). We evaluate NK amount, the balance of activating and inhibitory receptors (rp) of different sources, outcomes of KIR-AI UCB/BM. Methodology: NK UCB, BM, peripheral blood (PB) were evaluated by flow cytometry (CD3, 7, 16, 56, 94, NKG2A), KIR by PCR. Mathematical model was developed for evaluation the balance of activating and inhibitory rp as an index of cytotoxic activity (ICA) of mature NK. To select donor (dn) for KIR-AI we investigate med 3 samples (range 3-8) BM/UCB. The indication - salvage therapy, ECOG>3. BM-dn with low ICA were excluded. Lymphodepletion included CyFlu (up to 3 d), both BM (12 pts) and UCB (11 pts). Results: NK UCB ranged 5-56% (med 16) of lymphocytes. No any differences between NK -UCB and BM (similar to PB). For dn and pts no ICA differences by sex and age, ICA depend on depression and virus. For pts no ICA difference by type of cancer, germinal mutations, but strong correlation with nearest outcome of cancer. FU med 9 mo (2-52). OS (11 pts, 14 UCB-transfusions) med 6 mo (2+ -10), comparable to BM med 8 mo (2-48). AI outcomes depend on the intensity of lymphodepletion and ICA UCB/BM. Conclusion: Considering acceptable toxicity of lymphodepletion and good AI tolerability, including poor pts, the indications for cellular anticancer treatment could be expanded. We start pilot using UCB for KIR-AI for overcome chemoresistance and to achieve complete remission of disease after finishing anticancer treatment of solid tumors and for MRD-eradication in hematology. Additional undeniable advantage of UCB KIR-AI is quick availability of UCB from a KIR-typed UCB register.