Abstract 4830: Target-molecular specific near infrared cancer photoimmunotherapy: Detection, treatment, and monitoring of tumors with a theranostic fluorescent probe

Abstract

Abstract Targeted molecular therapies of cancer offer the possibility of effective tumor control with a minimum of side effects. However, to date this strategy has had modest results for most tumors. Antibody-based therapies have been among the more successful molecular approaches. The concept of using the antibody as a vector for additional therapy has been attempted with toxins and radio-isotopes with mixed results. Herein we describe an antibody conjugate with a photosensitive near infrared (NIR) phthalocyanine dye, IR700, which can be used as an optical imaging agent at low doses of light but becomes a photoimmunotherapeutic (PIT) at higher doses of light. In this study, we tested the efficacy of PIT with optimized regimen using an EGFR antbody-IR700 conjugate in a xenograft tumor model. For in vitro PIT, EGFR (HER1) expressing A431 cells were incubated with panitumumab-IR700 conjugates (Pan-IR700) which were then irradiated with NIR light. For in vivo PIT, A431 xenograft tumor bearing mice injected with 100 μg of Pan-IR700 every week. Mice were then treated with NIR light on day one (50 J cm−2) and day 2 (100 J cm−2) after Pan-IR700 injection which was administered every week for up to 4 weeks. NIR fluorescence images were obtained in each mouse and the effect of the PIT was analyzed. Pan-IR700 demonstrated specific binding to target receptors on the cell membrane. Target-specific cell death could be induced only in Pan-IR700 binding cancer cells immediately after exposure to NIR light. In vitro microscopy demonstrated that NIR exposure resulted in cellular swelling, bleb formation, and rupture of vesicles indicating necrotic cell death. No phototoxicity was observed in co-cultured HER1 negative Balb3T3 cells, even when MAb-IR700 was not removed from the medium. HER1 target-specific accumulation of MAb-IR700 was observed in mouse xenograft tumors by fluorescence imaging. Repeated administration of Pan-IR700 followed by repeated irradiation with NIR light resulted in effective tumor eradication and prolonged survival compared to control mice with no significant side effects. IR700 fluorescence from the conjugate allowed for image guidance of light delivery as well as monitoring of PIT. In conclusion, Pan-IR700 PIT was effective, only when the antibody conjugates were bound to the cell membrane, but showed no phototoxicity when they were not bound or irradiated with NIR light. Target selective PIT enables selective treatment of cancer with no apparent side effects even with multiple administrations of Pan-IR700 and NIR light irradiation. PIT using MAb-IR700 is a promising theranostics for highly selective treatment of cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4830. doi:1538-7445.AM2012-4830