Near-infrared Photoimmunotherapy Targeting Canine Mammary Tumors: Comparative Oncology for Overcoming Human Breast Cancer.

BACKGROUND/AIM: Human breast cancer is one of the most common cancer types in women. While surgery and radiation remain the mainstay of treatment, minimally invasive treatments are generally not considered sufficiently efficacious due to the invasive and potentially metastatic nature of the disease. Near-infrared photoimmunotherapy (NIR-PIT) is an emerging local cancer treatment that induces immunogenic cell death (ICD) and stimulates host immunity which could result in higher success rates than traditional ablative treatments. Accordingly, the clinical use of NIR-PIT for breast cancer is a potential avenue for exploration. This study evaluated the efficacy of NIR-PIT targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) using a canine mammary tumor (CMT) model.

MATERIALS AND

METHODS

The cytotoxic effects of NIR-PIT targeting EGFR and HER2 were evaluated in canine mammary cancer cell line, CMT-U27 and CF41.Mg. For detection of ICD, the expression of surface ICD markers, heat shock protein 70 and calreticulin, extra-cellular ATP release, and loss of nuclear protein was evaluated. The therapeutic effects of NIR-PIT targeting EGFR was assessed in the CMT-U27 tumor model.

RESULTS

NIR-PIT targeting EGFR and HER2 significantly decreased cellular viability and induced dramatic membrane damage in CMT cells. NIR-PIT increased surface markers of ICD as well as extracellular ATP release, and nuclear protein loss. In a CMT-bearing mouse model, NIR-PIT targeting EGFR significantly suppressed tumor growth and prolonged survival.

CONCLUSION

NIR-PIT is a potential therapeutic strategy for treating CMT and could be extended to the treatment of sporadic breast cancer in canines as an initial step prior to its use in humans.