Journal
CELL DEATH & DISEASE
Volume 11, Issue 10, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-020-03077-6
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Funding
- National Science Centre, Poland [2015/19/N/NZ7/01336, 2016/20/T/NZ7/00522]
- ICR
- NIHR Clinical Research Facility at the Royal Marsden, London, UK
- RM/ICR National Institute for Health Research Biomedical Research Centre
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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.
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