Adjuvant Type determines Preventive Cancer Vaccine Effect in Mouse Metastatic Breast Cancer Model

초록

Background Adjuvants function either by making antigen stay longer or by enhance innate immunity for the effective antigen specific vaccines. Currently, there are several types of adjuvants used, CpG (oligonucleotides), Alum (potassium aluminum sulfate), and MF59 (fish oil based). It is shown that various adjuvants can modulate host immune response types such as TH1 type with CpG, TH2 type with Alum, and TH1 and TH2 type with MF59. Although Korean Ginseng is well known for its boosting immune system, it still remains as questions how it functions. Methods To ask the effects and the basic mechanism of various adjuvants in cancer vaccine, we chose to utilize three mouse metastatic breast cancer models: 4T1+Balb/c model (TH2 host), EO771+C57BL/6 model (TH1 host), and MMTV-PyMT transgenic model spontaneously generating breast cancer. Mice were vaccinated three times at 3 weeks intervals with adjuvants and peptide derived from Prss14/Epithin, a critical marker for breast cancer. After vaccination, C57BL/6 and Balb/c models were injected with syngenic breast cancer cells. Vaccine effects were monitored by tumor size and the number of lung nodules. To determine the TH types, isotypes of antibody specific to Prss14/Epithin were screened. Innate immune cells in tumor tissues were analyzed by flow cytometry. Results Vaccination of antigenic Prss14/epithin peptide greatly reduced metastasis when it was injected with CFA/IFA in 4T1+Balb/c model and with alum or MF59 in EO771+C57BL/6 model. In both cases, TH1 and TH2 type responses were detected, but only in TH1 host, TH2 type antibodies showed significant reverse correlation to the metastasis events. In MMTV-PyMT model, only antigen with CFA/IFA showed beneficial for animals. Surprisingly, antigen with alum revealed adverse effect on tumor growth and metastasis. In the analysis of tumor tissue of immunized MMTV-PyMT, the proportion of eosinophil was increased significant only in the effective vaccine cases, suggesting tha