Impact of Vitamin C on Immune Response and Edema Following Near-Infrared Photoimmunotherapy (NIR-PIT)

Near-infrared photoimmunotherapy (NIR-PIT) is a recently approved cancer therapy utilizing an antibody conjugated to IR700 dye which is injected and then followed with focal NIR light. NIR-PIT is ideal for focal therapy of cancer because of its cell specificity and minimal invasiveness compared to surgical resection. Most treatment-emergent adverse events are low grade and include edema, fatigue, and pain. However, edema in specific anatomic locations could lead to significant complications, such as airway obstruction, and thus, it is desirable to reduce edema if possible. Edema and the resulting pain are likely precipitated by reactive oxygen species generated primarily from the interaction of laser light with unbound antibody-photoabsorber conjugate. These reactive species can be neutralized by reducing agents, such as vitamin C, a potent reducing agent and proton donor. Based on its photochemical mechanisms, we hypothesized that pretreating patients with L-sodium ascorbate (L-NaAA) will reduce NIR-PIT-induced edema. Here, we evaluated the effect of L-NaAA concentration on edema as well as its effect on the immune responses after NIR-PIT. L-NaAA demonstrated concentration-dependent inhibition of edema after NIR-PIT without compromising the efficacy of NIR-PIT. Furthermore, L-NaAA did not impede the anticancer immune activation elicited by NIR-PIT, nor did it affect the efficacy of Treg-targeted NIR-PIT. NIR-PIT groups, both with and without L-NaAA, significantly inhibited tumor growth and resulted in markedly prolonged survival compared to the control group, but those with L-NaAA had reduced edema. Thus, L-NaAA may serve as a useful adjunct to NIR-PIT, enhancing its safety profile without detracting from its therapeutic efficacy.