Immunomodulatory activity of IR700-labelled affibody targeting HER2.
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Embargo End Date
ICR Authors
Authors
Mączyńska, J
Da Pieve, C
Burley, TA
Raes, F
Shah, A
Saczko, J
Harrington, KJ
Kramer-Marek, G
Da Pieve, C
Burley, TA
Raes, F
Shah, A
Saczko, J
Harrington, KJ
Kramer-Marek, G
Document Type
Journal Article
Date
2020-10-20
Date Accepted
2020-10-01
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 (ZHER2:2395-IR700) selectively to induce cancer cell death in vitro and in vivo. The studies in vitro confirmed the specificity of ZHER2:2395-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 ZHER2:2395-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 ZHER2:2395-IR700 enhanced DC maturation, as indicated by augmented expression of CD86 and HLA-DR. In SKOV-3 xenografts, the ZHER2:2395-IR700-based phototherapy delayed tumour growth and increased median overall survival. Collectively, our results strongly suggest that ZHER2:2395-IR700 is a promising new therapeutic conjugate that has great potential to be applicable for photoimmunotherapy-based regimens.
Citation
Cell death & disease, 2020, 11 (10), pp. 886 - ?
Source Title
Publisher
SPRINGERNATURE
ISSN
2041-4889
eISSN
2041-4889
Research Team
Preclinical Molecular Imaging
Targeted Therapy
Preclinical Molecular Imaging
Targeted Therapy
Targeted Therapy
Preclinical Molecular Imaging
Targeted Therapy