SU2C-Lustgarten Foundation Translational Research Team: Chimeric Antigen Receptor T Cell (CAR T) Therapy for Pancreatic Cancer

Overview

Although the use of the patient’s immune cells to fight cancer in a therapeutic strategy called CAR-T therapy has been promising with blood cancers, it seems to be less effective in treating solid cancers. The goal of the SU2C-Lustgarten Foundation Chimeric Antigen Receptor T Cell (CAR T) Research Team is to understand why immunotherapy is not causing tumor regression in all patients. They study the genetic and epigenetic markings in CAR-T cells to identify characteristics to optimize the cancer-killing features of CAR T cells.

The research team’s focus is to use state-of-the-art epigenetic approaches and pre-clinical models to examine CAR-T cells and tumor cells in patients, especially pancreatic cancer patients, who respond, and in those who do not respond, to CAR-T therapy.

The team has two major aims:

1. To isolate CAR-T cells from patients with ovarian cancer, mesothelioma, and metastatic pancreatic cancer. The CAR-T cells will be analyzed using state of the art cellular assays.
2. To analyze the re-isolated CAR-T cells obtained from patients to understand how to prolong and enhance the activity of CAR-T cells. The team expects these studies to shed light on approaches to optimizing the combination of CAR-T cells with checkpoint therapies that block the function of CTLA-4 and PD-1.

Progress to Date:

The team has been able to successfully manufacture CAR-T cells from six mesothelioma and ovarian cancer patients, and safely treat the patients without overt off-tumor, on-target toxicity against normal tissues. The team confirmed that many CAR-T cells were able to home in on the tumor.

Funding

$2 million

Principals

Jos Melenhorst, PhD, University of Pennsylvania
Simon Lacey, PhD, University of Pennsylvania

Updated: May 2018