The induction of cytotoxic T cells and tumor regression by soluble antigen formulation.
CTLs specific for tumor antigens play a major role in the immunity against cancer. We have shown that class I-restricted CTLs can be induced by injecting soluble antigens mixed in an antigen formulation (AF) that consists of squalane, Tween 80, and Pluronic L121 (S. Raychaudhuri et al., Proc. Natl. Acad. Sci. USA, 89: 8308-8312, 1992). In this study, using ovalbumin and the ovalbumin-expressing transfectoma (EG7) as a tumor model system, we examined the in vivo antitumor effect of antigen-AF mixture. Vaccination of mice with ovalbumin in AF 2 or 3 days after EG7 tumor challenge showed significant inhibition of tumor growth compared to mice vaccinated with ovalbumin in alum or in saline. Depletion of CD8+ cells at the time of immunization completely abrogated the AF-induced tumor protection, indicating that CD8+ T cells are the major effectors in tumor protection in vivo. Depletion of CD4+ cells led to a marginal loss of tumor protection, which may be the result of inhibition of ovalbumin-specific CTL response due to the lack of T-helper activity. Our results demonstrate that AF can be used in subunit vaccines to stimulate CTLs and tumor regression in vivo.
Hariharan
K
K
IDEC Pharmaceuticals Corporation, San Diego, California 92121, USA.
Braslawsky
G
G
Black
A
A
Raychaudhuri
S
S
Hanna
N
N
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003902:Detergents; D005260:Female; D007111:Immunity, Cellular; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination / Q000379:methods
D003902:Detergents; D010047:Ovalbumin