1591 - Patritumab (anti-HER3 antibody) augments anti-tumor immune response of adoptive transfer of autologous activated T cells for patient-derived xenograft models of breast cancer.

Background

Signals of HER3/EGFR dimerization to PI3K/AKT/mTOR pathways are thought to be involved in cancer survival, proliferation and up-regulation of PD-L1 expression. We hypothesized that inhibition of the HER3 signal could enhance anti-tumor immunity by regulating the expression of PD-L1.

Methods

Two patient-derived xenograft (PDX) models of breast cancer were treated with patritumab (anti-HER3 antibody), polyclonal activated autologous T cells (PATCs) or a combination of patritumab and PATCs (P-PATCs). Tumor size was evaluated for anti-tumor effects of each treatment. To test immunological modulation by patritumab, tumors and liver tissue were immunohistochemically stained with anti-CD3, CD4, CD8, CD137 and PD-L1 antibody.

Results

Although treatment of PATCs or patritumab alone showed limited anti-tumor effects, P-PATCs treatment showed a significantly greater anti-tumor response in both PDX models. Interestingly, the proportion of CD137 expressing T cell infiltration was significantly higher in P-PATCs group compared to patritumab or the PATCs group, while the proportion of CD4+ T cell infiltration was also higher in the P-PATCs group. There were equal proportions of T cells without CD137 expression presented in liver tissues in both PATCs and P-PATCs groups.

Conclusions

These data suggest that patritumab could contribute to augmentation of antigen-specific T cell activation leading to additional anti-tumor effects on patritumab treatment alone by means of immunological mechanisms. Thus, inhibition of HER3/neuregulin (ligand for HER3) signal might be of interesting concept for both regulation of oncologic signal and immunological modulation in HER3-expressing breast cancer.

Clinical trial identification

Legal entity responsible for the study

Eiji Suzuki.

Funding

Daiichi Sankyo Company.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.