Table 2.
Articles on PCI of cytotoxic therapeutics reviewed in this paper.
| Author, Year, Country | Tested Tissue/Cells | PCI-Internalized Molecule and Photosensitizer | Study Model | Primary Outcome | Reference |
|---|---|---|---|---|---|
| PRECLINICAL STUDIES | |||||
| Olsen et al., 2013 | Dox-resistant human sarcoma cell line MES-SA/Dx5 and non-resistant MES-SA line | rGel and TPCS2a | In vitro: Cell culture | PCI circumvents the mechanisms of PDT resistance in dox-resistant human sarcoma cell lines | [25] |
| O’Rourke et al., 2017 | Rat cortical mixed glial cells, DRG, and satellite glia, HNSCC cell line | Bleomycin and TPPS2a or TPCS2a | In vitro: Cell culture | DRG neurons can survive TPCS2a and TPPS2a-mediated PCI at doses enough to kill the carcinoma cell line | [26] |
| Martínez-Jothar et al., 2019 | Human HER2+ and HER2− breast cancer cell lines |
Saporin or placebo in PEGylated NP and TPPS2a, functionalized with 11A4 nanobody | In vitro: Cell culture | PCI of saporin-loaded PEGylated NP can be used to selectively induce cell death of HER2+ breast cancer cells | [27] |
| Norum et al., 2017 | Murine CC and murine MGC cells in athymic and thymic BALB/c mice | Bleomycin and AlPcS2a | In vivo: Murine allograft model | PCI of bleomycin had a curative effect on tumor cells in thymic, but not in athymic mice and induced immune responses sufficient to reject new tumor cells for up to two months | [28] |
| Stratford et al., 2013 | Human sarcoma cell line and human fibrosarcoma cell line, human sarcoma cells in athymic nude mice | CD133-targeting immunotoxins and TPCS2a | In vitro: Cell culture In vivo: Murine xenograft model |
Proof-of-concept: PCI of CD133-targeting immunotoxins reduces cellular viability and proliferative capacity of sarcoma cells and inhibits tumor grafting | [29] |
| Bostad et al., 2015 | Human CA, ALL, malignant melanoma, and TNBC (CD133+ and CD133−) cell lines, human CA cells in athymic nude mice | CD133-targeting immunotoxin and TPCS2a | In vitro: Cell culture In vivo: Murine xenograft model |
Efficient PCI of CD133-targeting immunotoxins in human cancer cell lines in vitro. Proof-of-concept: Anti-tumor response after PCI of CD133-targeting immunotoxins in vivo |
[30] |
| Eng et al., 2018 | Human TNBC, amelanotic human melanoma, human Melmet cell lines, amelanotic human melanoma cells in athymic nude mice | CSPG4-targeting toxin and TPCS2a | In vitro: Cell culture In vivo: Murine xenograft model |
PCI of CSPG4-based immunotoxins induces death of CSPG4-positive and drug-resistant cells of TNBC and malignant melanoma origin, in vitro and in vivo | [32] |
| Berstad et al., 2015 | Head and neck squamous cell carcinoma cell line. A-431or SCC-026 cells in athymic nude mice | rGel/EGF (an EGFR-targeted fusion protein) | In vitro: Cell culture In vivo: Murine xenograft model |
PCI increased the cytotoxicity of rGel/EGF in EGFR-expressing cells. PCI of rGel/EGF induced significant antitumor effects in A-431 xenograft mice | [31] |
| Weyergang et al., 2018 | VEGFR2-expressing endothelial cells, murine colon carcinoma, and breast carcinoma cell lines in vitro and in BALB/c and athymic nude mice | VEGF121/rGel and TPPS2a (in vitro) or TPCS2a (in vivo) | In vitro: Cell culture In vivo: Murine allograft model |
PCI of VEGF121/rGel directly targets tumor cells and induces T-cell mediated tumor remission, reduced perfusion, and produced tumor protection in vivo | [63] |
| CLINICAL TRIALS IN HUMAN | |||||
| Sultan et al., 2016, England | Patients (18 to 85 years) with local recurrent, advanced, or metastatic cutaneous or subcutaneous malignancies | Bleomycin and TPCS2a | Phase I, First-in-human |
Administration of TPCS2a was found to be safe and tolerable by all patients. No significant systemic adverse events related to photochemical internalization treatment occurred. | [52,64] |
| Jerjes et al., 2019, England | 57-year-old male with end-stage recurrent and therapy-resistant chondroblastic osteosarcoma in the right mandible | Bleomycin and TPCS2a | Case report | Illuminated areas responded favorably to treatment. PCI anti-tumor activity was superior to PDT, clinically and histopathologically. Peri-illumination pain | [65] |
Dox: Doxorubicine. DRG: dorsal root ganglion neurons. HNSCC: head and neck squamous cell carcinoma. NP: Nanoparticles. CC: Colon carcinoma. MGC: Mammary gland carcinoma. CA: Colorectal adenocarcinoma. ALL: Acute lymphocytic leukemia. TNBC: Triple negative breast cancer. CSPG4: cell surface chondroitin sulfate proteoglycan 4. rGel: recombinant Gelonin. EGFR: epidermal growth factor receptor.