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Targeting CD276 for T cell-based immunotherapy of breast cancer.

Authors :
Hagelstein I
Wessling L
Rochwarger A
Zekri L
Klimovich B
Tegeler CM
Jung G
Schürch CM
Salih HR
Lutz MS
Source :
Journal of translational medicine [J Transl Med] 2024 Oct 04; Vol. 22 (1), pp. 902. Date of Electronic Publication: 2024 Oct 04.
Publication Year :
2024

Abstract

Background: Breast cancer (BC) is the most common malignancy in women. Immunotherapy has revolutionized treatment options in many malignancies, and the introduction of immune checkpoint inhibition yielded beneficial results also in BC. However, many BC patients are ineligible for this T cell-based therapy, others do not respond or only briefly. Thus, there remains a high medical need for new therapies, particularly for triple-negative BC. CD276 (B7-H3) is overexpressed in several tumors on both tumor cells and tumor vessels, constituting a promising target for immunotherapy.<br />Methods: We analyzed tumor samples of 25 patients using immunohistochemistry to assess CD276 levels. The potential of CC-3, a novel bispecific CD276xCD3 antibody, for BC treatment was evaluated using various functional in vitro assays.<br />Results: Pronounced expression of CD276 was observed in all analyzed tumor samples including triple negative BC. In analyses with BC cells, CC-3 induced profound T cell activation, proliferation, and T cell memory subset formation. Moreover, treatment with CC-3 induced cytokine secretion and potent tumor cell lysis.<br />Conclusion: Our findings characterize CD276 as promising target and preclinically document the therapeutic potential of CC-3 for BC treatment, providing a strong rationale for evaluation of CC-3 in BC patients in a clinical trial for which the recruitment has recently started.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
1479-5876
Volume :
22
Issue :
1
Database :
MEDLINE
Journal :
Journal of translational medicine
Publication Type :
Academic Journal
Accession number :
39367484
Full Text :
https://doi.org/10.1186/s12967-024-05689-4