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-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.
Highlights
Cancer immunotherapy continues to gain recognition as an oncology treatment as new and improved cancer vaccines and other immunostimulants are produced
Increasing the SDS concentration of the buffer 10-fold to disrupt the covalent bonds had little effect; the vaccine still yielded a complex vaccine profile even on nonbiotinylated tumors. These findings indicate that streptavidin has a high affinity for the bound tumor proteins
Vaccine [50]–treated rats demonstrated approximately six times lower reactivity to streptavidin than the streptavidin-only and Vaccine [100] groups. These results suggest that the level of streptavidin antibody response is modulated by both the streptavidin dose and the reduced tumor proteins in the vaccine
Summary
Cancer immunotherapy continues to gain recognition as an oncology treatment as new and improved cancer vaccines and other immunostimulants are produced. Using a patient's own tumor proteins to produce a vaccine is an attractive concept, and a number of autologous vaccines are undergoing preclinical evaluation [1]. Other immune therapies, such as dendritic cell therapy, have moved into the clinic, but while they increase survival time in patients they do not initiate immunologic rejection or remission of a tumor [2, 3]. Induction of immunologic rejection and remission remains the holy grail of cancer therapy. Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).
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