Stem Cell Research & Therapy (Aug 2024)

Cytokine-induced killer cells: new insights for therapy of hematologic malignancies

  • Faezeh Ghanbari Sevari,
  • Amir Mehdizadeh,
  • Khadijeh Abbasi,
  • Seyyed Sina Hejazian,
  • Mortaza Raisii

DOI
https://doi.org/10.1186/s13287-024-03869-z
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 21

Abstract

Read online

Abstract Background Cytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC‐unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment‐related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies. Main body CIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3−/CD56+ NK cells, and CD3+/CD56− cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary effectors. Compared with the previously reported antitumor immune cells, CIK cells are characterized by improved in vitro proliferation and amplification, enhanced migration and invasive capacity to tumor region, more significant antitumor activity, and a broader antitumor spectrum. CIK cells can also induce death in tumor cells via numerous pathways and mechanisms. Hence, CIKs-based therapy has been used in various clinical trials and has shown efficacy with a very low graft versus host disease (GVHD) against several cancers, such as hematologic malignancies, even in relapsing cases, or cases not responding to other therapies. Despite the high content of T cells, CIK cells induce low alloreactivity and, thus, pose a restricted threat of GVHD induction even in MHC-mismatched transplantation cases. Phase 1 and 2 clinical trials of CIK cell therapy have also highlighted satisfactory therapeutic advantages against hematologic cancers, indicating the safety of CIK cells even in haploidentical transplantation settings. Conclusion CIK cells have shown promising results in the treatment of hematologic malignancies, especially in combination with other antitumor strategies. However, the existing controversies in achieving desired clinical responses underscore the importance of future studies.

Keywords