Journal Article

DKFZ-2024-01058

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The bispecific B7H3xCD3 antibody CC-3 induces T cell immunity against bone and soft tissue sarcomas.

Holzmayer, S.DKFZ* ; Liebel, K.DKFZ* ; Hagelstein, I.DKFZ* ; Salih, H. R.DKFZ* ; Märklin, M.DKFZ*

2024
Frontiers Media Lausanne

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Please use a persistent id in citations: doi:10.3389/fimmu.2024.1391954

Abstract: Sarcomas are rare and heterogeneous malignancies that are difficult to treat. Approximately 50% of patients diagnosed with sarcoma develop metastatic disease with so far very limited treatment options. The transmembrane protein B7-H3 reportedly is expressed in various malignancies, including different sarcoma subtypes. In several cancer entities B7-H3 expression is associated with poor prognosis. In turn, B7-H3 is considered a promising target for immunotherapeutic approaches. We here report on the preclinical characterization of a B7-H3xCD3 bispecific antibody in an IgG-based format, termed CC-3, for treatment of different sarcoma subtypes. We found B7-H3 to be expressed on all sarcoma cells tested and expression on sarcoma patients correlated with decreased progression-free and overall survival. CC-3 was found to elicit robust T cell responses against multiple sarcoma subtypes, resulting in significant activation, release of cytokines and effector molecules. In addition, CC-3 promoted T cell proliferation and differentiation, resulting in the generation of memory T cell subsets. Finally, CC-3 induced potent target cell lysis in a target cell restricted manner. Based on these results, a clinical trial evaluating CC-3 in soft tissue sarcoma is currently in preparation.

Keyword(s): Humans (MeSH) ; Antibodies, Bispecific: pharmacology (MeSH) ; Antibodies, Bispecific: therapeutic use (MeSH) ; Sarcoma: immunology (MeSH) ; Sarcoma: drug therapy (MeSH) ; B7 Antigens: immunology (MeSH) ; B7 Antigens: metabolism (MeSH) ; T-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: metabolism (MeSH) ; Cell Line, Tumor (MeSH) ; Bone Neoplasms: immunology (MeSH) ; Bone Neoplasms: pathology (MeSH) ; Female (MeSH) ; Male (MeSH) ; Animals (MeSH) ; Lymphocyte Activation: immunology (MeSH) ; Middle Aged (MeSH) ; CD3 Complex: immunology (MeSH) ; Aged (MeSH) ; Cell Proliferation (MeSH) ; Adult (MeSH) ; B7-H3 ; CD276 ; T cell engager ; bispecific antibody ; sarcoma ; CD276 protein, human

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Tübingen (TU01)

Research Program(s):

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

Appears in the scientific report 2024

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

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