Enhancing the efficacy of near-infrared photoimmunotherapy through intratumoural delivery of CD44-targeting antibody- photoabsorber conjugates

Background Photoimmunotherapy (PIT) is a potent modality for cancer treatment. The conventional PIT regimen involves the systemic delivery of an antibody-photoabsorber conjugate, followed by a 24-h waiting period to ensure adequate localisation on the target cells. Subsequent exposure to near-infrared (NIR) light selectively damages the target cells. We aimed to improve the efficacy of PIT in vivo by evaluating the effects of the different routes of conjugate administration on treatment outcomes. Methods Subcutaneous Lewis lung carcinoma tumours were established in mice, targeting cluster of differentiation (CD)44 with an anti-CD44 antibody conjugated to IRDye700DX (IR700). The conjugate was administered via the intravenous or intratumoural route followed by the assessment of antibody binding and therapeutic effects of PIT. Findings Compared to intravenous administration, intratumoural delivery of the CD44-IR700 conjugate significantly increased the number of cells binding to the conjugate by >five-fold. This method, combined with NIR light irradiation, halved tumour growth when compared to intravenous delivery. Reducing the interval between intratumoural injection and NIR light exposure to 30 min did not diminish efficacy, thereby demonstrating the feasibility of a 1-h procedure. Interpretation Intratumoural administration of the antibody-photoabsorber conjugate enhanced the efficacy of PIT in vivo. A simplified, 1-h procedure involving conjugate tumour injection followed by irradiation emerged as a potent cancer treatment strategy.