Selection of antibody and light exposure regimens alters therapeutic effects of EGFR-targeted near-infrared photoimmunotherapy.
Ryuhei OkadaTakuya KatoAki FurusawaFuyuki InagakiHiroaki WakiyamaDaiki FujimuraShuhei OkuyamaHideyuki FurumotoHiroshi FukushimaPeter L ChoykeHisataka KobayashiPublished in: Cancer immunology, immunotherapy : CII (2022)
Near-infrared photoimmunotherapy (NIR-PIT) is a cell-specific cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. Intravenously injected APC binds the target cells, and subsequent NIR light exposure induces immunogenic cell death only in targeted cells. Panitumumab and cetuximab are antibodies that target human epidermal growth factor receptor (hEGFR) and are suitable for NIR-PIT. In athymic nude mouse models, panitumumab-based NIR-PIT showed superior therapeutic efficacy compared to cetuximab-based NIR-PIT because of the longer half-life of panitumumab-IR700 (pan-IR700) compared with cetuximab-IR700 (cet-IR700). Two light exposures on two consecutive days have also been shown to induce superior effects compared to a single light exposure in the athymic nude mouse model. However, the optimal regimen has not been assessed in immunocompetent mice. In this study, we compared panitumumab and cetuximab in APCs for NIR-PIT, and single and double light exposures using a newly established hEGFR-expressing cancer cell line derived from immunocompetent C57BL/6 mice (mEERL-hEGFR cell line). Fluorescence imaging showed that the decline of pan-IR700 was slower than cet-IR700 confirming a longer clearance time. Among all the combinations tested, mice receiving pan-IR700 and double light exposure showed the greatest tumor growth inhibition. This group was also shown to activate CD8 + T lymphocytes in lymph nodes and accumulate CD8 + T lymphocytes to a greater extent within the tumor compared with the control group. These results showed that APCs with longer half-life and double light exposure lead to superior outcomes in cancer cell-targeted NIR-PIT in an immunocompetent mouse model.
Keyphrases
- fluorescence imaging
- wild type
- photodynamic therapy
- cancer therapy
- metastatic colorectal cancer
- mouse model
- epidermal growth factor receptor
- drug release
- fluorescent probe
- cell death
- drug delivery
- induced apoptosis
- lymph node
- cell cycle arrest
- small cell lung cancer
- tyrosine kinase
- air pollution
- locally advanced
- endothelial cells
- stem cells
- radiation therapy
- early stage
- adipose tissue
- advanced non small cell lung cancer
- squamous cell carcinoma
- lymph node metastasis
- endoplasmic reticulum stress