W. Nathaniel Brennen

About W. Nathaniel Brennen

T cells are a type of immune cell with significant tumor cell seeking and killing capabilities, but tumor survival mechanisms cause T cell inactivation. Methods for re-arming these specialized killing cells provides powerful treatment opportunities.

Dr. Nathaniel Brennen will engineer a patient’s T cells to act as “Trojan horses”: specifically targeting tumor cells and releasing a cell wall-damaging bacterial toxin, proaerolysin (PA), to kill the tumor cells.

A patient’s T cells will be transformed with a CAR molecule, an engineered T cell-activating and targeting molecule that recognizes a tumor-associated protein, PSMA. When the CAR-T cell locates its target (PSMA), the T cell will be activated to release the toxin.

PSMA can be expressed by normal brain and kidney cells. To avoid non-specific toxicity, the toxin will be delivered in a modified inactive form, and can only be converted to its active form by a prostate-specific enzyme, prostate-specific antigen (PSA).

Dr. Brennen’s strategy will result in the development of a highly specific and highly toxic live cell therapy for the treatment of prostate cancer.

What this means for patients: What this means for patients: While significant advances have been made in the development of prostate cancer therapies, patients will eventually become resistant and progress to a lethal disease state. If successful, this project will develop an innovative and powerful new treatment strategy that uses the patient’s immune system to kill tumor cells.