Adoptive Cell Therapy in Pediatric Leukemia
Abstract
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are the two common types of pediatric leukemia. Despite conventional therapy, treatment failure and poor survival are observed in children with leukemia. Adoptive cell therapy needs to get more advanced to overcome high-risk pediatric leukemia. Dendritic Cells and cytokines are two influential factors in natural killer (NK) cell therapy. However, no defined effect of killer-cell immunoglobulin-like receptor (KIR) on NK cells has been obtained. Moreover, a combination of checkpoint fusion protein with chimeric antigen receptor (CAR) T-cell therapy can highly improve the anti-tumor function of T cells. Biomarkers, namely serum cytokines, MicroRNAs (miRs), ADAM6, CD200 and CD123, sGRP78 and CXCR4, and Semaphorin 4D (Sema4D) are helpful in finding patients with a risk of relapse, and an appropriate treatment approach, or act as a potential targetable marker. In this review, the clinical and preclinical/animal studies with the purpose of diagnosis and treatment of relapsed or refractory pediatric leukemia are discussed. Preclinical/animal ACT studies have shown improvements in the treatment of children with high-risk leukemia. However, clinical studies are required to verify the efficacy of these approaches for the treatment of childhood leukemia.
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8. Korotchkina L, Kazyulkin D, Komarov PG, Polinsky A, Andrianova EL, Joshi S, et al. OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis. Leukemia. 2020;34(7):1828–39.
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10. Handgretinger R, Lang P, Andre MC. Exploitation of natural killer cells for the treatment of acute leukemia. Blood. 2016;127(26):3341–9.
11. Kimpo MS, Oh B, Lee S. The role of natural killer cells as a platform for immunotherapy in pediatric cancers. Curr Oncol Rep. 2019;21(10):93.
12. Barrett DM, Singh N, Porter DL, Grupp SA, June CH. Chimeric antigen receptor therapy for cancer. Annu Rev Med. 2014;65:333.
13. Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A. 1993;90(2):720–4.
14. Restifo SA, Rosenberg NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Cancer Immunol Immunother. 2015.
15. Sprangers B, Van Wijmeersch B, Fevery S, Waer M, Billiau AD. Experimental and clinical approaches for optimization of the graft-versus-leukemia effect. Nat Clin Pract Oncol. 2007;4(7):404–14.
16. Moretta L, Bottino C. Natural killer cells: a mystery no more. Scand J Immunol. 2002.
17. Bottino C, Castriconi R, Pende D, Rivera P, Nanni M, Carnemolla B, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med. 2003;198(4):557–67.
18. Moretta A. Activating receptors and coreceptors. Annu Rev Immunol. 2001.
19. Reizis B. Plasmacytoid dendritic cells: development, regulation, and function. Immunity. 2019;50(1):37–50.
20. Collin M, Bigley V. Human dendritic cell subsets: an update. Immunology. 2018;154(1):3–20.
21. Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN, et al. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014;15(7):e257–67.
22. Van Eck Van Der Sluijs J, Van Ens D, Thordardottir S, Vodegel D, Hermens I, et al. Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses. Cancer Immunol Immunother. 2021;70(11):3167–81.
23. Liu S, Dhar P, Wu JD. NK cell plasticity in cancer. J Clin Med. 2019;8(9):1492.
24. Romee R, Schneider SE, Leong JW, Chase JM, Keppel CR, Sullivan RP, et al. Cytokine activation induces human memory-like NK cells. Blood. 2012;120(24):4751–60.
25. Song Y, Hu B, Liu Y, Jin Z, Zhang Y, Lin D, et al. IL-12/IL-18-preactivated donor NK cells enhance GVL effects and mitigate GvHD after allogeneic hematopoietic stem cell transplantation. Eur J Immunol. 2018;48(4):670–82.
26. Romee R, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses. 2016.
27. Tanzi M, Consonni M, Falco M, Ferulli F, Montini E, Pasi A, et al. Cytokine-induced memory-like NK cells with high reactivity against acute leukemia blasts and solid tumor cells suitable for adoptive immunotherapy approaches. Cancers (Basel). 2021;13(7):1687.
28. Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol. 2005;5(3):201–14.
29. Leung W. Use of NK cell activity in cure by transplant. Br J Haematol. 2011;155(1):14–29.
30. Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, et al. Human diversity in killer cell inhibitory receptor genes. Immunity. 1997;7(6):753–63.
31. Uhrberg M, et al. Human KIR repertoires: shaped by genetic diversity and evolution. 2015.
32. Koltan S, Koltan A, Soszynska K, Matiakowska K, Morgut-Klimkowska M, Grzesk E, et al. Killer-cell immunoglobulin-like receptor genotype and haplotype combinations in children treated for acute lymphoblastic leukemia. Cent Eur J Immunol. 2021;46(2):210–6.
33. Verneris MR, Miller JS, Hsu KC, Wang T, Sees JA, Paczesny S, et al. Investigation of donor KIR content and matching in children undergoing hematopoietic cell transplantation for acute leukemia. Blood Adv. 2020;4(7):1350–6.
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| Files | ||
| Issue | Vol 8, No 1 (2025) | |
| Section | Review Article | |
| DOI | https://doi.org/10.18502/igj.v8i1.17992 | |
| Keywords | ||
| Adoptive Cell Therapy Biomarker CAR T-Cell Therapy NK-Cell Therapy Pediatric Leukemia | ||
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How to Cite
1.
Sadeghi M, Asnaashari K. Adoptive Cell Therapy in Pediatric Leukemia. Immunol Genet J. 2025;8:39-49.
