Abstract 5253: Epigenetic drugs partially restored anti-cholangiocarcinoma activity of dysfunctional CD3+CD56+ cells

Abstract The cholangiocarcinoma cell-exposed cytokine-induced killer (CIK) cells or their most efficacious CD3+CD56+ subset displayed weaken anti-tumor cytotoxicity upon subsequent exposure. RNAseq analysis of the resistant phenotype gave rise to a list of drugs that could potentially counter the activity of genes associated with resistance to the anti-tumor activity of CIK cells. The top-ranking drugs appeared to be epigenetic drugs. Sublethal concentration of these drugs were assayed for their synergistic activity with CIK cell or the CD3+CD56+ subset for cytolysis of resistant CCA cells in tissue culture model. These drugs, although in low concentration, contained anti-tumor activity. The tumor cytolysis was greater after the combination with either CIK cells or the CD3+CD56+ subset. An in vivo model of CCA-implanted mice exhibited the synergistic activity of subtherapeutic dose of these drugs and CD3+CD56+ subset in suppressing tumor growth. It is concluded that epigenetic drugs in subtherapeutic dose could prevent the dysfunction of CCA-exposed CIK cells. Citation Format: Adisak Wongkajornsilp, Porncheera Chusorn, Kriengkrai Phongkitkarun, Khin Su Su Htwe, Sunisa Duangsa-ard, Kanda Kasetsinsombat, Nathawadee Sawatpiboon. Epigenetic drugs partially restored anti-cholangiocarcinoma activity of dysfunctional CD3+CD56+ cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5253.