Abstract P5-01-11: A new anti-HER2 peptide “CH401MAP” can stimulate the immunity of breast cancer patients
Authors: Tsuda B , Kametani Y , Ohgiya R , Oshitanai R , Terao M , Terada M , Morioka T , Niikura N , Okamura T , Saito Y , Suzuki Y , Tokuda Y 
Published: August 2014

In previous decades, numerous attempts have been made to develop therapeutic peptide vaccines for cancer. However, the HLA (Human Leukocyte Antigen) types are limited because most peptide vaccines are specific to the major HLA types of the area. Peptide vaccines specific for Caucasians thus may not be specific to Japanese. Moreover, they are not designed to stimulate both helper and killer T cells. We are trying to make a peptide vaccine specific to the MHC of Japanese patients that stimulates both helper and killer T cells. We selected a new-HER2 peptide including a B-cell epitope which has anti-tumor effects in a mouse system. The B-cell epitope was determined for a H401 monoclonal antibody (mAb) specific for HER2. As for epitope mapping of the chimera mAb CH401, enzyme-linked immunosorbent assay was employed with 20mer MAPs carrying a partial HER2 sequence. The CH401 epitope was determined as N:163-182, and the CH401MAP including the epitope induced anti-tumor effects in HER2-overexpressing tumor cells in a mouse system. We predicted the peptide MHC affinity and examined the in vitro reaction of PBMCs from Japanese breast cancer patients. The study enrolled 173 female breast cancer patients who underwent surgery between October 2010 and July 2012 at Tokai University Hospital. We used SYFPEITHI, BIMAS and IEDB algorithms to estimate peptide and HLA affinity. Lymphocyte proliferation ability, cell surface marker expression, cytokine (interleukin (IL)-2, IL-4 and interferon (IFN)-g) secretion and specific antibody production were analyzed in vitro. According to the algorithms, 97.1% of patients showed high to intermediate affinity of the CH401 epitope peptide to Japanese major HLA class I. Similarly, 34.5% of patients showed high to moderate affinity to HLA class II. The proliferative ability of patient groups was significantly higher than that of the HD group (HER2 0 group, p&lt;0.05; HER2 1+2+ group, p&lt;0.01; HER2 3+ group, p&lt;0.01). Cell percentages of CD8+ cells were significantly increased after 21 days of CH401MAP stimulation. In the HER2 0 patient group, CD4+CD25+ cell ratio was also increased, while no significant increase was seen in the other groups. Foxp-3 expression was not increased in any groups, suggesting that these cells were not regulatory T cells. Concentrations of IL2 in stimulated supernatant tended to increase in all patient groups. In particular, concentration in the HER2 1+2+ group at 48 h was significantly increased (p&lt;0.001). IL-4 and IFN-g secretion also tended to increase. CH401MAP-specific antibodies were measured for all breast cancer patient groups and HD, showing significant differences. However, within each patients’ group, no significant differences were observed irrespective of CH401MAP stimulation (p&lt;0.001). As a result, reactivity with CH401MAP and breast cancer patient PBMCs activated immunity in the total breast cancer patient group, and the association with HER2 expression level of the primary cancer was poor overall. Collectively, CH401MAP may become a promising peptide vaccine to prevent recurrent breast cancer in Japanese patients.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-01-11.