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

E. John Wherry, PhD
Co-leader

E. John Wherry, PhD

University of Pennsylvania

Shelley L. Berger, PhD
Co-leader

Shelley L. Berger, PhD

University of Pennsylvania

Carl H. June, MD
Leader

Carl H. June, MD

University of Pennsylvania

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