Lesion-Targeted Anti-Cancer Gene Delivery with Clinical Survival Benefits: A Molecular “Rosetta Stone” for Veterinary Hematology-Oncology and Precision Gene Therapy

Abstract

This review represents a series of medical hematology-oncology papers by Gordon, Chawla and Hall, composed with the following intents and purposes: (i) documenting significant milestones in Tumor Targeting and Cancer Gene Therapy for the postmodern biomedical and veterinary research communities, (ii) honoring forthright principles of scientific responsibility, regulatory oversight, and informed consent, which serve to protect both human and companion animal health, and (iii) translating FDA-qualified, updated methods & compositions (CMC and cGMP insights) to veterinary medicine, in light of recent critical analyses, hence gains, in long-term cancer-free survival data achieved in humans. The focus is on tumor-targeted, injectable gene therapy vectors and molecular approaches developed by Gordon and Hall at USC / Children's Hospital Los Angeles-validating "Pathotropic" (disease-seeking) tumor targeting Avant la Lettre. The discussion provides clinical insights into the cellular and molecular mechanisms of both tumor-targeting and tumor-eradication, which led to the formal return of Rexin-G as DeltaRex-G from industrial desuetude to cGMP bioproduction in 2018-2019, with FDA Expanded Access, under a decidedly academic non-profit banner, in accord with historic U.S. "Right-to-Try" legislation. In the spirit of academic fellowship and the interests of a rightfully concerned society, this article provides a molecular (cellular and genetic) "Rosetta Stone" for the responsible translation and biotechnology transfer of these clinically validated U.S. FDA-evolved Pathotropic (i.e., disease-seeking) tumor targeting Methods and Compositions safely to Veterinary Medicine as preclinical safety and efficacy studies in mice, rats, rabbits, minipigs and monkeys were required by the USFDA prior to authorization to use DeltaRex-G in first-in-human clinical trials.