Project Grant R01CA297896

This federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $602,881 to Duke University for the development and testing of novel immunotherapies using optimized tumor cell-penetrating antibodies. The primary objective is to translate these innovative antibody-based therapies into the clinic to effectively combat aggressive, mutation-driven human cancers.

The key products or services to be delivered under this 5-year award include:

1. Elucidating the mechanisms governing the effectiveness of newly engineered IgG antibodies that can penetrate cancer cells and neutralize common oncogenic mutations like KRAS. The researchers will select a lead candidate antibody for clinical development.
2. Defining how the transcytosis (cellular transport) of these IgG antibodies impacts T cell-dependent anti-tumor immunity, and identifying safe interventions that can synergize with the antibody therapy.
3. Determining whether the tumor cell-penetrating antibodies can overcome resistance to small molecule inhibitors across various cancer mutations, establishing the range of human cancers sensitive to this new immunotherapy approach.

This research aims to bridge existing knowledge gaps regarding transcytosing antibodies and pave the way for a new generation of effective immunotherapies to combat aggressive, mutation-driven cancers.