TY - JOUR
T1 - A single photodynamic priming protocol augments delivery of ⍺-PD-L1 mAbs and induces immunogenic cell death in head and neck tumors*
AU - Bhandari, Chanda
AU - Moffat, Azophi
AU - Fakhry, John
AU - Malkoochi, Ashritha
AU - Nguyen, Austin
AU - Trinh, Brian
AU - Hoyt, Kenneth
AU - Story, Michael D.
AU - Hasan, Tayyaba
AU - Obaid, Girgis
N1 - Publisher Copyright:
© 2023 The American Society for Photobiology.
PY - 2023
Y1 - 2023
N2 - Photodynamic priming (PDP) leverages the photobiological effects of subtherapeutic photodynamic therapy (PDT) regimens to modulate the tumor vasculature and stroma. PDP also sensitizes tumors to secondary therapies, such as immunotherapy by inducing a cascade of molecular events, including immunogenic cell death (ICD). We and others have shown that PDP improves the delivery of antibodies, among other theranostic agents. However, it is not known whether a single PDP protocol is capable of both inducing ICD in vivo and augmenting the delivery of immune checkpoint inhibitors. In this rapid communication, we show for the first time that a single PDP protocol using liposomal benzoporphyrin derivative (Lipo-BPD, 0.25 mg/kg) with 690 nm light (75 J/cm2, 100 mW/cm2) simultaneously doubles the delivery of ⍺-PD-L1 antibodies in murine AT-84 head and neck tumors and induces ICD in vivo. ICD was observed as a 3–11 fold increase in tumor cell exposure of damage-associated molecular patterns (Calreticulin, HMGB1, and HSP70). These findings suggest that this single, highly translatable PDP protocol using clinically relevant Lipo-BPD holds potential for improving immunotherapy outcomes in head and neck cancer. It can do so by simultaneously overcoming physical barriers to the delivery of immune checkpoint inhibitors, and biochemical barriers that contribute to immunosuppression.
AB - Photodynamic priming (PDP) leverages the photobiological effects of subtherapeutic photodynamic therapy (PDT) regimens to modulate the tumor vasculature and stroma. PDP also sensitizes tumors to secondary therapies, such as immunotherapy by inducing a cascade of molecular events, including immunogenic cell death (ICD). We and others have shown that PDP improves the delivery of antibodies, among other theranostic agents. However, it is not known whether a single PDP protocol is capable of both inducing ICD in vivo and augmenting the delivery of immune checkpoint inhibitors. In this rapid communication, we show for the first time that a single PDP protocol using liposomal benzoporphyrin derivative (Lipo-BPD, 0.25 mg/kg) with 690 nm light (75 J/cm2, 100 mW/cm2) simultaneously doubles the delivery of ⍺-PD-L1 antibodies in murine AT-84 head and neck tumors and induces ICD in vivo. ICD was observed as a 3–11 fold increase in tumor cell exposure of damage-associated molecular patterns (Calreticulin, HMGB1, and HSP70). These findings suggest that this single, highly translatable PDP protocol using clinically relevant Lipo-BPD holds potential for improving immunotherapy outcomes in head and neck cancer. It can do so by simultaneously overcoming physical barriers to the delivery of immune checkpoint inhibitors, and biochemical barriers that contribute to immunosuppression.
KW - head and neck cancer
KW - immune checkpoint blockade
KW - immunogenic cell death
KW - photodynamic priming
KW - tumor delivery
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U2 - 10.1111/php.13865
DO - 10.1111/php.13865
M3 - Article
C2 - 37818742
AN - SCOPUS:85173688190
SN - 0031-8655
JO - Photochemistry and Photobiology
JF - Photochemistry and Photobiology
ER -