Immunomodulatory activity of IR700-labelled affibody targeting HER2

Abstract

Abstract There is an urgent need to develop therapeutic approaches that can increase the response rate to immuno-oncology agents. Photoimmunotherapy has recently been shown to generate anti-tumour immunological responses by releasing tumour-associated antigens from ablated tumour cell residues, thereby enhancing antigenicity and adjuvanticity. Here, we investigate the feasibility of a novel HER2-targeted affibody-based conjugate (Z HER2:2395 -IR700) selectively to induce cancer cell death in vitro and in vivo. The studies in vitro confirmed the specificity of Z HER2:2395 -IR700 binding to HER2-positive cells and its ability to produce reactive oxygen species upon light irradiation. A conjugate concentration- and light irradiation-dependent decrease in cell viability was also demonstrated. Furthermore, light-activated Z HER2:2395 -IR700 triggered all hallmarks of immunogenic cell death, as defined by the translocation of calreticulin to the cell surface, and the secretion of ATP, HSP70/90 and HMGB1 from dying cancer cells into the medium. Irradiating a co-culture of immature dendritic cells (DCs) and cancer cells exposed to light-activated Z HER2:2395 -IR700 enhanced DC maturation, as indicated by augmented expression of CD86 and HLA-DR. In SKOV-3 xenografts, the Z HER2:2395 -IR700-based phototherapy delayed tumour growth and increased median overall survival. Collectively, our results strongly suggest that Z HER2:2395 -IR700 is a promising new therapeutic conjugate that has great potential to be applicable for photoimmunotherapy-based regimens.