Grant: Project Grant

Radiation therapy, chemotherapy, and surgery are the most common cancer treatments in the past decade. These treatments are not targeted to specific cancer cells and can cause significant damage to normal tissues. Developments in the fields of molecular imaging and radio-immunotherapies are enabling the development on new theranostic agents that are used both diagnostics, patient stratification, therapy, and response monitoring. Antibodies are integral for the development of theranostics directed to cancer markers. We propose to develop theranostics against a tumor-associated molecule that is present on the membrane of a broad number of cancer types. This molecule, referred to as Neu5Gc GM3, cannot be produced by human cells, but is produced by most agricultural animals and thus is incorporated into cancer cells via diet. Cancer cells can preferentially pick up Neu5Gc due to the exceptional ability of tumors to ingest it from the blood relative to normal tissues. We will generate and evaluate molecular theranostics using a human antibody, 14F7hT, which specifically recognizes Neu5Gc GM3 ganglioside. We will attach radioactive emitting molecules to 14F7hT to generate nuclear imaging probes. We will attach beta-particle emitters to 14F7hT to generate radio-theranostics. We will evaluate these molecular theranostics using cancer cell lines and cancer mouse models for imaging and therapy.