Streptavidin: A Novel Immunostimulant for the Selection and Delivery of Autologous and Syngeneic Tumor Vaccines

Abstract

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-a was upregulated in vaccine-treated rats, whereas ICAM1 was downregulated. After engraftment, vaccinated rats maintained CD4þ 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.

The principles and applications of avidin-based nanoparticles in drug delivery and diagnosis

“…Streptavidin bound to biotinylated soluble tumor proteins have successfully produced tumor reduction and remission in a 9L glioma rat model and in canine patients. [82]…”

CD71 targeting boosts immunogenicity of sublingually delivered influenza haemagglutinin antigen and protects against viral challenge in mice

“…A factor, other than increased bioavailability of antigen, which could have contributed towards overcoming tolerance is the presence of streptavidin within our conjugate vaccine. Although not measured in this study, streptavidin and streptavidin conjugates can elicit anti-streptavidin antibodies and can feasibly act as an adjuvant in promoting the immunogenicity of the vaccine formulations, after the vaccine cargo crosses the mucosal surface [28]. Therefore it is possible that in addition to the CD71 transport capabilities, the presence of streptavidin in the vaccine formulation further enhanced the immunogenic nature of the formulation.…”

Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model

“…Further, the assay can also be used to assess the immunological response to different therapies. Previously we have used this assay to monitor the response to an anti-cancer vaccine therapy in a syngeneic glioma model (9L) 22 . In that study, CD4 and CD8 T cells were the most informative markers.…”