A murine monoclonal anti-idiotype (Id) antibody, 3H1 has been developed and characterized previously. Anti-Id 3H1 mimics a specific
epitope of
carcinoembryonic antigen (CEA) and can be used as a surrogate
antigen for CEA. 3H1 induced anti-CEA immunity in different species of animals as well as humans and showed promise as a potential
vaccine candidate in phase I/II clinical trials for
colon cancer patients. One area of interest to us has been the development of new immune adjuvants that may augment the potency of 3H1 as a
tumor vaccine.
Oligodeoxynucleotides containing unmethylated CpG motifs (
CpG ODN) are potent immunostimulatory agents capable of enhancing the Ag-specific Th1 response when used as immune adjuvants. In this study, we have evaluated the efficacy of 3H1 as a
tumor vaccine when admixed with a select
CpG ODN 1826 in transgenic mice that express human CEA. The
vaccine potential of 3H1 was also assessed in the presence of another widely used adjuvant,
QS-21. 3H1 coupled to
keyhole limpet hemocyanin (KLH) and mixed with
Freund's adjuvant (FA) was used as a gold standard in this system. 3H1 vaccination with different adjuvants induced both humoral and cellular anti-3H1, as well as anti-CEA immunity in CEA transgenic mice. The
immune sera could lyse CEA-transfected murine colon
carcinoma cells, C15 effectively in an antibody-dependent cellular cytotoxicity assay. The anti-CEA antibody responses were somewhat comparable in each adjuvant-treated group of mice, whereas cellular immune responses were significantly greater when CpG was used as an adjuvant. Splenocytes obtained from 3H1-CpG-immunized mice showed an increased proliferative CD4(+) Th1-type T-cell response when stimulated in vitro with 3H1 or CEA and secreted elevated levels of Th1
cytokines (IL-2, IFN-gamma). This
vaccine also induced MHC
class I antigen-restricted CD8(+) T-cell responses. In a solid
tumor model, C15
tumor growth was significantly inhibited by 3H1 vaccinations. In 3H1-CpG-vaccinated mice, the duration of survival was, however, longer compared to the 3H1-QS21-vaccinated mice. These findings suggest that 3H1-CpG vaccinations can break peripheral tolerance to CEA and induce protective antitumor immunity in this murine model transgenic for human CEA.