Poster abstracts

Poster number 112 submitted by Zhantao Du

Humanized anti-SSTR2-MMAF antibody-drug conjugate for the treatment of meningioma

Zhantao Du (Molecular, Cellular, and Developmental Biology Graduate Program), Margaret Liu (Chemical and Biomolecular Biological Engineering)

Abstract:
Meningiomas account for over 38% of primary central nervous system tumors, yet there is no effective treatment strategy for inoperable or high-grade cases. Somatostatin receptor 2 (SSTR2), highly expressed in meningiomas, represents a promising therapeutic target. We developed and humanized an anti-SSTR2 monoclonal antibody, and conjugated it with monomethyl auristatin F to generate an antibody-drug conjugate (ADC). The preclinical evaluations with flow cytometry, confocal microscopy, in vivo imaging system, cytotoxicity assay and Western blotting demonstrated that the anti-SSTR2 ADC selectively targets meningioma and inhibits the proliferation of tumor cells effectively. The in vivo evaluations using intracranially xenografted meningioma mouse models showed that 12 or 24 mg/kg of ADC reduced tumor burden and prolonged survival with minimal toxicity in normal tissues. The post treatment histology analysis revealed proliferation inhibition and apoptosis induction. This study suggested that the humanized anti-SSTR2 ADC has great potential to treat meningioma.

References:
Chen K, Si Y, Ou J, Guan JS, Kim S, Ernst P, Zhang Y, Zhou L, Han X, Liu XM. Antibody-Drug Conjugate to Treat Meningiomas. Pharmaceuticals (Basel). 2021 May 2;14(5):427. doi: 10.3390/ph14050427. PMID: 34063284; PMCID: PMC8147502.

Keywords: SSTR2, ADC, Meningioma