decitabine + NK cell infusion

Decitabine + NK cell infusion is a combination therapy that pairs the hypomethylating agent decitabine with adoptively transferred natural killer (NK) cells. This approach aims to enhance anti-tumor responses through multiple mechanisms. Decitabine, a DNA methyltransferase inhibitor, reverses hypermethylation-induced gene silencing, potentially sensitizing cancer cells to immune attack. When combined with NK cell infusion, decitabine has been shown to positively modulate NK cell maturation, cytolytic functions, and trafficking to tumor sites[1][6]. The therapy typically involves administering decitabine for several days (often 5-10 days), followed by infusion of NK cells, which may be derived from various sources including CD34+ progenitors or haploidentical donors. In some protocols, additional agents like interleukin-2 (IL-2) are administered to facilitate NK cell survival and expansion[4][7]. Clinical trials have investigated this combination primarily for acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN), particularly in relapsed/refractory settings or as consolidation therapy[4][7][9]. ## Mechanism of Action Decitabine works by inhibiting DNA methyltransferase, leading to DNA hypomethylation and reactivation of silenced genes. This can restore normal cellular functions including proliferation control and apoptosis sensitivity in cancer cells[8]. When combined with NK cells, decitabine has been shown to: 1. Sensitize AML cells to NK cell-mediated killing 2. Enhance NK cell maturation and cytolytic functions 3. Improve NK cell trafficking and accumulation at tumor sites 4. Potentially increase the expression of activating ligands on tumor cells[1] Studies have demonstrated that decitabine, but not azacitidine (another hypomethylating agent), specifically potentiates the anti-leukemic activity of NK cells, suggesting a unique synergy between decitabine and NK cell therapy[1][6].