Phase I study of TNFα AutoVaccIne in Patients with metastatic cancer

We evaluated the safety and immunogencity of a novel vaccine directed against autologous TNFα in a Phase I fixed dose escalation trial. The vaccine consisted of two recombinant TNFα proteins, with specific peptides replaced by foreign immunodominant T cell epitopes from tetanus toxoid. The main objectives were to establish a safe dose and evaluate the vaccines ability to raise neutralising TNFα antibodies. Secondary objectives were improvements in body weight and tumour response. Thirty-three patients were vaccinated with three doses (20, 100, or 400 μg) of TNFα vaccine at 2-weekly intervals adjuvanted with aluminium hydroxide. Anti-TNFα antibody titres were measured by both a RIA, using soluble native TNFα as the antigen, and by an ELISA using immobilized partly denatured TNFα. Eleven patients (33%) had mild grade1/2 injection site reactions at the higher doses. In 10 of 20 patients, serum antibodies recognize denatured TNFα in the ELISA, whereas, antibody titres against native TNFα in the RIA were undetectable. This suggests that the production process had partly denatured the vaccine preventing the formation of cross-reacting antibodies to native TNFα. In conclusion, TNFα vaccine was able to elicit vaccine specific antibodies. However, since the antibodies were only able to cross-react with partly denatured TNFα, evaluation of safety and tumour responses to the TNFα vaccine was compromised.