title: 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-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.
authors.affiliation: Authors' Affiliations: Small Animal Specialist Hospital, Sydney, New South Wales, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Weir
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Hudson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Moon
authors.forename: Angus
authors.initials: A
authors.lastname: Ross
authors.forename: Miles
authors.initials: M
authors.lastname: Alexander
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Peters
authors.forename: Veronika
authors.initials: V
authors.lastname: Langova
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clarke
authors.forename: Nick
authors.initials: N
authors.lastname: Pavlakis
authors.forename: Ross
authors.initials: R
authors.lastname: Davey
authors.forename: Viive M
authors.initials: VM
authors.lastname: Howell
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005910:Glioma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D051381:Rats; D019809:Streptavidin / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D019809:Streptavidin