Targeting Monoclonal Antibodies to the Tumor Microenvironment for Cancer Therapy/Immunotherapy
Frederick L. Hall1, Sant P. Chawla2, Neal S. Chawla2, Erlinda M. Gordon1,2*
Affiliation
- 1Counterpoint Biomedica LLC, Santa Monica CA 90403, USA
- 2Sarcoma Oncology Center/Cancer Center of Southern California, Santa Monica CA 90403, USA
Corresponding Author
Erlinda M. Gordon, 2811 Wilshire Blvd., Suite 414, Santa Monica CA 90403, USA; Tel: 818-726-3278; E-mail: erlinda.gordon@gmail.com
Citation
Gordon, EM., et al. Targeting Monoclonal Antibodies to the Tumor Microenvironment for Cancer Therapy / Immunotherapy (2016) Cell Immunol Serum Biol 2(1): 20- 26.
Copy rights
Copy rights: ©2016 Gordon, EM. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Keywords
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.
