Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun 6;26(12):5428.
doi: 10.3390/ijms26125428.

The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy

Varvara Maiorova  1 , Murad D Mollaev  1 , Polina Vikhreva  1 , Alexey Kibardin  1 , Michael A Maschan  1 , Sergey S Larin  1
Affiliations
Review

The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy

Varvara Maiorova et al. Int J Mol Sci. .

Abstract

Recently, the chimeric antigen receptor (CAR)-T approach represented a breakthrough in the treatment of B-cell malignancies, encouraging the application of the approach for other hematological diseases, such as acute myeloid leukemia (AML). Heterogeneity and antigen variation in the pathological cell population hinder the choice of molecular targets in the case of AML. In this review, the critical aspects were described that are usually considered when selecting molecular targets for the new CAR genetic constructs. The role of AML-associated antigens in AML progression was covered. In conclusion, we proposed an approach that may allow the elimination of pathological cells in AML more effectively.

Keywords: CAR T; acute myeloid leukemia; target choice.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Challenges of molecular target choice for CAR-T cells in AML. (A) Heterogeneity of blast cells limits the effectiveness of CAR-T cell therapy of AML. (B) The AML-associated antigens are often expressed by the healthy cells, leading to CAR-T-mediated on-target off-tumor toxicity. CAR; chimeric antigen receptor. AML; acute myeloid leukemia.
Figure 2
Figure 2
Heterogenic blast population in AML may be targeted with a cocktail of CAR-Ts, each specific to an AML-associated antigen expressed by a pathological subpopulation.
See this image and copyright information in PMC

References

    1. Wang M. CAR T-Cell Therapy Effective in B Acute Lymphoblastic Leukaemia. Lancet Oncol. 2017;18:e314. doi: 10.1016/S1470-2045(17)30364-9. - DOI - PubMed
    1. Bhaskar S.T., Dholaria B., Savani B.N., Sengsayadeth S., Oluwole O. Overview of Approved CAR-T Products and Utility in Clinical Practice. Clin. Hematol. Int. 2024;6:108–114. doi: 10.46989/001c.124277. - DOI - PMC - PubMed
    1. Ryan C. FDA Approves Obecabtagene Autoleucel for Adults with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. FDA; Silver Spring, MD, USA: 2024.
    1. Albelda S.M. CAR T Cell Therapy for Patients with Solid Tumours: Key Lessons to Learn and Unlearn. Nat. Rev. Clin. Oncol. 2024;21:47–66. doi: 10.1038/s41571-023-00832-4. - DOI - PubMed
    1. Hemminki K., Zitricky F., Försti A., Kontro M., Gjertsen B.T., Severinsen M.T., Juliusson G. Age-Specific Survival in Acute Myeloid Leukemia in the Nordic Countries through a Half Century. Blood Cancer J. 2024;14:44. doi: 10.1038/s41408-024-01033-7. - DOI - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources