Near-Infrared Photoimmunotherapy for Cancers of the Gastrointestinal Tract

Abstract

<b><i>Background:</i></b> Cancers of the gastrointestinal (GI) tract are the common leading cause of cancer-related death in the world. Recent advances in cancer therapies such as intensive multidrug chemotherapy and molecular targeted treatment have improved therapeutic efficacy; however, the outcomes are not satisfied. Moreover, these therapies also cause severe side effects. New type of cancer therapies is urgently needed to improve the outcomes and to reduce side effects of GI tract cancers. <b><i>Summary:</i></b> This account is a comprehensive review article on the newly developed, photochemistry-based cancer therapy named as near-infrared photoimmunotherapy (NIR-PIT). NIR-PIT is a highly selective tumor treatment that employs an antibody-photoabsorber conjugate, which is activated by near-infrared light. A world-wide phase 3 clinical trial of NIR-PIT against recurrent head and neck cancer patients is currently underway. NIR-PIT differs from conventional cancer therapies such as surgery, chemotherapy, and radiation in its selectivity for killing cancer cells and cells treated with NIR-PIT leading to immunogenic cell death. Preclinical research in animals with combining cancer-targeting NIR-PIT and other cancer immunotherapies could lead to responses not only in local tumor but also in distant metastases. NIR-PIT also leads to an immediate and dramatic increase in vascular permeability after therapy. From these aspects, NIR-PIT appears to be a promising new form of cancer therapy. NIR-PIT could be readily translated into clinical use for virtually any cancers in the near future provided suitable humanized antibodies are available. Here, we describe the specific advantages and applications of NIR-PIT in the GI tract. <b><i>Key Messages:</i></b> We believe that NIR-PIT with NIR excitation light, which can be delivered via a fiber optic diffuser through endoscopes, is a promising method for a new treatment of GI cancers.