Growth Factor Imaging and Photoimmunotherapy

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

This project spans many parts of the molecular imaging program. We have been and continue to be focused on developing membrane receptor targeted agents in order to diagnose, stage and select patients for therapy. In addition to the agents described above, one other class of imaging agents is based on antibodies. We have developed multiple radiolabeled antibodies and have completed several clinical trials involving them. In addition we have developed a novel therapy called photoimmunotherapy (PIT) that conjugates a specific photon absorbing dye, IR700 to an antibody. This antibody photon absorber conjugate (APC) is then injected and binds to the cognate receptor on the tumor cell surface. Exposure to near infrared light (NIR) produces a rapid and selective cancer cell killing. PIT was discovered by our team in 2010 and multiple animal models were undertaken. By 2013 the invention was licensed to Aspyrian which is now Rakuten. Over the past several years Phase 1 and Phase II studies in head and neck cancers have been performed with a 44% objective response rate in recurrent head and neck cancers. Several long term survivors have been seen. PIT is now in global Phase 3 testing and was approved in Japan in late 2020. Meanwhile we are developing PIT that targets immunosuppressive cells in the hopes of promoting an even stronger immune response than is evoked by PIT of the tumor. When, for instance, Treg PIT is combined with anti tumor PIT in mouse models strong immunogenic responses are seen with induction of memory T cells preventing further implantation of the tumor. We are studying this phenomenon in mouse models at the microscopic level to better understand how removing T reg cells from the tumor microenvironment specifically causes T cell mediated cell killing. At the same time we continue as a program to develop targeted small molecule and antibody conjugates for PET imaging. We are initiating a clinical trial in the CC NIH to use PIT as a neoadjuvant therapy prior to surgery in patients with operable head and neck cancers. A CD25 antibody for killing Treg cells has been developed and is currently being manufactured for use in human trials. This agent, when combined with a tumor targeted PIT will cause a substantial increase in the immune response to PIT leading to more profound treatment effects.