TARGETING MONOCLONAL ANTIBODIES TO THE TUMOR MICROENVIRONMENT FOR CANCER THERAPY/IMMUNOTHERAPY
Journal: Journal of Cellular Immunology and Serum Biology (Vol.2, No. 1)Publication Date: 2016-05-02
Authors : Erlinda Gordon;
Page : 1-7
Keywords : Monoclonal Antibodies; Immune Checkpoint Inhibitors; Tumor- Targeting; Targeted Drug Delivery; Tumor Microenvironment; Extracellular Matrix;
Abstract
Background: Therapeutic antibodies and immune checkpoint inhibitors can be delivered more efficiently to the tumor microenvironment (TME) by targeting the exposed collagenous (XC) proteins at the site[s] of tumor invasion, stroma formation, and neoangiogenesis. Purpose: To assess the ability of bifunctional fusion polypepetides (mAb-Tropins) to selectively deliver monoclonal antibodies (mAbs) to the TME in tumor-bearing nude mice. Methods: Synthetic peptide probes and polypeptide aptamers (25- 50 aa), fluorescein -labeled IgGs, and an anti-VEGF human mAb were tested in vitro in exposed collagen (XC)-agarose binding assays, in HUVEC cultures, and in vivo in a human xenograft model of pancreatic cancer in nude mice. Results: The XC-targeted mAb-Tropins, bound non-covalently to FITC-labeled IgGs [but not to truncated F(Ab')2 fragments], and exhibited selectivity for XC-agarose over control agarose matrices. Importantly, the biological activity of the XC/mAb-Tropinbound anti-VEGF mAbs was fully preserved, as demonstrated by inhibition of endothelial cell proliferation in HUVEC cultures. In vivo, intense fluorescence was observed in tumors of mice injected with mAb-Tropin targeted IgGs at 15 and 60 minutes after intravenous injection, but not in non-targeted IgG-treated mice. Conclusions: Tumor XC-targeted mAb-Tropins are an effective method of delivering therapeutic mAbs precisely to the tumor compartments, with meaningful implications for cancer therapy/immunotherapy.
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