Journal Article

DKFZ-2026-01081

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png B7-H3 (CD276) as Target for T Cell-Based Bispecific Antibody Therapy of Penile Cancer.

Kielbik, A. ; Bahlinger, V. ; Schürch, C. M. ; Barcena, M. L. ; Vakhrusheva, O. ; Thomas, A. ; Tsaur, I. ; Heitmann, J. S. ; Salih, H. R.DKFZ* ; Hagelstein, I.DKFZ*

2026
Dove Medical Press Ltd Auckland

Abstract: Metastatic or locally advanced penile cancer (PeCa) has limited systemic treatment options and a 5-year survival rate of ~10% in metastatic disease. Using the in vitro and ex vivo models we preclinically assessed CC-3, a B7-H3xCD3 bispecific antibody (bsAb) currently in a Phase I basket trial (NCT05999396).Primary PeCa cells were isolated from surgical specimens and characterized for surface antigen expression by flow cytometry (n = 4). B7-H3 expression was additionally evaluated in primary penile cancer tissues by immunohistochemistry (n = 10). The functional activity of the bsAb CC-3 was assessed in co-culture assays with PBMC, analyzing cytotoxicity, cytokine release, and T cell activation.Immunohistochemistry of tumors from ten PeCa patients revealed strong and consistent B7-H3 (CD276) expression, with a mean H-score of 200, in tumor cells and tumor-associated vasculature, potentially enhancing T cell influx upon targeting. In vitro and ex vivo co-cultures of primary PeCa cells with peripheral blood mononuclear cells from healthy donors and PeCa patients showed that CC-3 robustly activated CD4⁺ and CD8⁺ T cells, as defined by upregulation of CD69 and CD25, with donor-dependent kinetics. CC-3 also induced potent tumor cell lysis and T cell proliferation across all patient-derived tumor samples, whereas the isotype control had no effect, confirming target-restricted activity.These results demonstrate the strong immunostimulatory capacity of CC-3 and validate B7-H3 as a relevant target for T cell-based immunotherapy in PeCa. Our findings support the ongoing inclusion of PeCa patients in the clinical CC-3 trial and encourage further development of B7-H3-directed strategies for this rare, understudied malignancy.

Keyword(s): B7-H3 ; CD276 ; CD3 ; T cell ; bispecific antibody ; immunotherapy ; penile cancer

Note: #DKTKZFB26#

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Tübingen (TU01)
2. DKTK TU Translationale Immunologie (TU02)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Emerging Sources Citation Index ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Web of Science Core Collection

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