Full chimaeric CAR.CIK from patients engrafted after allogeneic haematopoietic cell transplant: Feasibility, anti-leukaemic potential and alloreactivity across major human leukocyte antigen barriers

Br J Haematol. 2023 Jan;200(1):64-69. doi: 10.1111/bjh.18469. Epub 2022 Sep 26.

Abstract

Cytokine-induced killer lymphocytes (CIK) are a promising alternative to conventional donor lymphocyte infusion (DLI), following allogeneic haematopoietic cell transplantation (HCT), due to their intrinsic anti-tumour activity and reduced risk of graft-versus-host disease (GVHD). We explored the feasibility, anti-leukaemic activity and alloreactive risk of CIK generated from full-donor chimaeric (fc) patients and genetically redirected by a chimeric antigen receptor (CAR) (fcCAR.CIK) against the leukaemic target CD44v6. fcCAR.CIK were successfully ex-vivo expanded from leukaemic patients in complete remission after HCT confirming their intense preclinical anti-leukaemic activity without enhancing the alloreactivity across human leukocyte antigen (HLA) barriers. Our study provides translational bases to support clinical studies with fcCAR.CIK, a sort of biological bridge between the autologous and allogeneic sources, as alternative DLI following HCT.

Keywords: AML; CAR; HSC transplantation; cell therapy; cytokine-induced killer lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Feasibility Studies
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / therapy
  • HLA Antigens
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Antigens Class II
  • Humans
  • Immunotherapy, Adoptive
  • Receptors, Chimeric Antigen*
  • Transplantation, Homologous

Substances

  • Receptors, Chimeric Antigen
  • HLA Antigens
  • Histocompatibility Antigens Class II