Cancer immunotherapy by intratumoral injection of α-gal glycolipids

Aim/Background: To determine the feasibility and safety of intratumoral α-gal glycolipids injection for conversion of human tumors into autologous Tumor Associated Antigens (TAA) vaccine. α-Gal glycolipids bind anti-Gal - the most abundant antibody in humans. Preclinical studies indicated that injected α-gal glycolipids insert into tumor cell membranes, bind anti-Gal and target tumor cells to Antigen Presenting Cells, thereby converting tumors into autologous TAA vaccines. We hypothesized that α-gal glycolipids might have similar utility in humans. Patients and Methods: Eleven patients with advanced solid tumors received one intratumoral injection of 0.1 mg, 1 mg, or 10 mg α-gal glycolipids. The primary endpoint was dose-limiting toxicity (DLT) within 4 weeks. Secondary endpoints included long-term toxicity, autoimmunity, radiological tumor response and survival. Results: There were no DLT and no clinical or laboratory evidence of autoimmunity, or any other toxicity. Few patients had an unexpectedly long survival. Conclusion: Intratumoral injection of α-gal glycolipids is feasible and safe for inducing a protective anti-tumor immune response.