monomethylauristatin-f has been researched along with Carcinoma--Squamous-Cell* in 1 studies
1 other study(ies) available for monomethylauristatin-f and Carcinoma--Squamous-Cell
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Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer.
Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression. The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was potently cytotoxic to cancer cells highly expressing GPC1. There were no inhibitory effects on cancer cells with low expression of GPC1. In a murine xenograft model, GPC1-ADC also had significant and potent tumor growth inhibition. GPC1-ADC-mediated G2/M phase cell cycle arrest was detected, indicating that the dominant antitumor effect in vivo was MMAF-mediated. The toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our data showed that GPC1-ADC has potential as a promising therapy for uterine cervical cancer. Topics: Adult; Aged; Animals; Antibodies, Monoclonal; Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Proliferation; Female; Glypicans; Humans; Immunoconjugates; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Middle Aged; Molecular Targeted Therapy; Oligopeptides; Prognosis; Tumor Cells, Cultured; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays; Young Adult | 2018 |