RT Journal Article
SR Electronic
T1 Streptavidin: A Novel Immunostimulant for the Selection and Delivery of Autologous and Syngeneic Tumor Vaccines
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
SP 469
OP 479
DO 10.1158/2326-6066.CIR-13-0157
VO 2
IS 5
A1 Weir, Chris
A1 Hudson, Amanda L.
A1 Moon, Elizabeth
A1 Ross, Angus
A1 Alexander, Miles
A1 Peters, Lyndsay
A1 Langova, Veronika
A1 Clarke, Stephen J.
A1 Pavlakis, Nick
A1 Davey, Ross
A1 Howell, Viive M.
YR 2014
UL http://cancerimmunolres.aacrjournals.org/content/2/5/469.abstract
AB Induction of antitumor immunity using 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) using streptavidin in combination with reduced soluble tumor proteins. Initial syngeneic vaccine studies in the 9L rat glioma model were used to optimize vaccine dose and selectivity. Cytokine and blood analysis was used to monitor the response. Rats receiving two vaccinations of syngeneic tumor vaccine demonstrated a statistically significant (P < 0.05) survival advantage compared with controls (adjuvant only). Notably, vaccination also led to remission rates of between 30% and 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 the response. The cytokine TNF-α was upregulated in vaccine-treated rats, whereas ICAM1 was downregulated. After engraftment, vaccinated rats maintained CD4+, CD8+ T cells, and total lymphocyte levels closer to normal baseline than those in the controls. Twenty-five dogs treated with autologous vaccine preparations using 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 using 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. Cancer Immunol Res; 2(5); 469–79. ©2014 AACR.