Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines

Abstract

Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS2a combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.

Photocontrolled apoptosis induction using precursor miR-664a and an RNA carrier-conjugated with photosensitizer

“…The PCI method can effectively deliver targeted molecules to the targeted cells. For instance, pre-clinical studies suggest that PCI can effectively deliver chemotherapeutic agents into tumor cells and improve treatment efficacy 6 . Thus, a PCI strategy will likely develop as an effective cancer therapy.…”

“…PCI, which uses a photosensitizer and harmless light, delivers targeted molecules such as drugs, peptides, and nucleic acids into the cytosol 6 – 8 . We developed a PCI-based apoptosis-inducing molecule, TatBim-Alexa.…”

Photodynamic Therapy (PDT) in Oncology

“…Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines: Šoši´c et al performed a review on the state of the art in photochemical internalization (PCI), a technology employed for the cytosolic release of chemotherapeutic agents or antigens [ 15 ]. Molecules such as chemicals, proteins, DNA or RNA are internalized by cells via endocytosis of phagocytosis.…”

Photochemical Internalization Enhanced Vaccination Is Safe, and Gives Promising Cellular Immune Responses to an HPV Peptide-Based Vaccine in a Phase I Clinical Study in Healthy Volunteers

“…Light-controlled activation of the photosensitizer results in reactions with molecular oxygen (O 2 ) and generation of reactive oxygen species (ROS) (11). These ROS species can induce lipid peroxidation and permeabilization of the vesicle membranes, ultimately leading to the release of the endosomal content into the cytosol [reviewed in (12,13)]. The fimaporfin photosensitizer is also used to enhance the efficacy of cytotoxic drugs, and is under clinical development for cancer therapy (14).…”