Biomedicines, 2025, 13(9):2130

Comparative Preclinical Analysis of Anti-B7-H3 CAR-T Cells Targeting Neuroblastoma

Background: Neuroblastoma is a childhood tumor that is usually fatal after relapse in high-risk patients. Most clinical trials of CAR-T therapy for neuroblastoma are based on targeting the disialoganglioside GD2. B7-H3, a protein from the immunoglobulin superfamily, is a specific marker for neuroblastoma and a number of other solid tumors. We conducted a preclinical study of three variants of anti-B7-H3 CAR-T cells in order to justify the selection of the best candidate for subsequent clinical trials. Methods: The expression level of B7-H3 was measured in a number of cell lines and neuroblastoma tissue samples via flow cytometry. The functional activity of CAR-T cells was compared using an NFAT-inducible reporter assay, a cytotoxicity test, cytokine production, and a repeated stimulation assay. Results: The obtained CAR-T cells carrying all resulting CAR variants specifically recognized and killed B7-H3-positive tumor cells in vitro. Nevertheless, TE9-28z and 8H9-28BBz demonstrated superior activation and cytokine production compared to the second-generation 8H9-BBz construct. TE9-28z and 8H9-28BBz exhibited functional differences in expansion, exhaustion markers, and cytokine secretion in co-cultures with target cells in vitro. In particular, TE9-28z induced higher IFNγ production, while 8H9-28BBz showed increased TNFα release. Despite comparable cytotoxicity, TE9-28z and 8H9-28BBz CAR-T cells exhibited varying persistence depending on the tumor type, and showed signs of functional exhaustion upon prolonged exposure to the target antigen. Conclusion: TE9-28z and 8H9-28BBz were selected for further preclinical development as promising candidates for the effective targeting of B7-H3-expressing malignancies.

Lutskovich DV, Meleshko AN, Stepanova VM, Dormeshkin DO, Rubtsov YP

Department of Peptide and Protein Technologies, Laboratory of biocatalysis, Department of functioning of living systems, Laboratory of molecular virology

: 10.3390/biomedicines13092130
Scopus: 2-s2.0-105017169344
: 41007693
IBCH: 12131
Ссылка на статью в журнале: https://www.mdpi.com/2227-9059/13/9/2130
Нет данных о цитировании
Данные статьи проверены модераторами 2025-10-23

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