Induction of anti-tumor immunity utilizing autologous tumor proteins is an attractive approach to cancer therapy. However, better methods and stimulants to present these autologous proteins back to the immune system are needed. Here we identify streptavidin as a novel carrier protein and stimulant and test the efficacy of both syngeneic (rat) and autologous vaccines (dogs) utilising streptavidin in combination with reduced soluble tumor proteins. Initial syngeneic vaccine studies in the 9L rat glioma model were used to optimise vaccine dose and selectivity. Cytokine and blood analysis was used to monitor the response. Rats receiving two vaccinations of syngeneic tumor vaccine demonstrated a significant (P<0.05) survival advantage compared with controls (adjuvant only). Notably, vaccination also led to remission rates of between 30 to 60% in the aggressive 9L glioma model. Antibodies to streptavidin were detected in the serum of vaccinated rats however antibody levels did not correlate with response. The cytokine TNFΒ was upregulated in vaccine treated rats while ICAM1 was down regulated. Post-engraftment, vaccinated rats maintained CD4+, CD8+ T cells and total lymphocyte levels closer to normal baseline than controls. Twenty five dogs treated with autologous vaccine preparations utilising streptavidin as a stimulant showed no adverse reactions, irrespective of additional chemotherapy and other medications. In this study we developed a novel method for producing syngeneic and autologous vaccines utilising streptavidin selectivity and immunogenicity. These vaccines show efficacy in the 9L glioma rat model. Safety was also demonstrated in canine patients presenting with cancer treated with autologous vaccine.
- Received September 18, 2013.
- Revision received January 28, 2014.
- Accepted January 31, 2014.
- Copyright © 2014, American Association for Cancer Research.