Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast Cancer: Optimizing the Conjugate-Light Regimen

摘要: Aim Triple-negative breast cancer (TNBC) is considered one of the most aggressive subtypes cancer. Near infrared photoimmunotherapy (NIR-PIT) a treatment that employs an antibody-photosensitizer conjugate (APC) followed by exposure NIR light for activating selective cytotoxicity on targeted cells and may have application to TNBC. In order minimize dose APC while maximizing therapeutic effects, dosing need be optimized. this study, we investigate in vitro vivo efficacy cetuximab (cet)-IR700 NIR-PIT two models MDAMB231 (TNBC, EGFR moderate) MDAMB468 high) cell lines, demonstrate method optimize light. Method After validating cell-specific cytotoxicity, effects were investigated mouse using lines derived from TNBC tumors. Tumor-bearing mice separated into 4 groups following treatments: (1) no (control); (2) 300 μg cet-IR700 i.v., (APC i.v. only); (3) only, was administered at 50 J/cm2 day 1 100 2 (NIR (4) after injection (one shot NIR-PIT). To compare different regimens with fixed APC, added treatments (5) immediately NIR-PIT, then 2, which performed times every week (“two split” NIR-PIT) (6) three per (“three NIR-PIT). Result Both specific binding greater than vitro. Tumor accumulation tumors significantly higher (p < 0.05) vivo. growth survival tumor bearing lower group 0.05). mice, improved all NIR-PIT; p 0.05, “two 0.01, “three 0.001) compared control groups. Conclusion NIR-PIT effective regardless expression EGFR, however, killing shown regimens, suppressed growth, resulting prolonged further splitting repeated exposures.