GRANTEE: Claudia Gravekamp, PhD
Albert Einstein College of Medicine
Co-Principal Investigator: Jennifer Chuy, MD, Montefiore Medical Center
Research Project: Improving Cancer Immunotherapy and Gemcitabine Sensitivity through Listeria
Award: 2016 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2016 – June 30, 2018
Dr. Gravekamp is an associate professor in the department of microbiology and immunology at Albert Einstein College of Medicine. She completed her undergraduate and master’s training at State University of Leiden, and her PhD at Erasmus University of Rotterdam, both in the Netherlands. Dr. Gravekamp has 15 years of experience in developing and testing mouse and human DNA-based and Listeria (bacteria)-based vaccines against cancer in various metastatic mouse tumor models of breast and pancreatic cancer, and in tumor immunology in mice and humans.
Dr. Chuy is an assistant professor in the department of medicine at Albert Einstein College of Medicine and the coordinator of cancer registry quality, cancer committee, at the Montefiore Medical Center at Albert Einstein College of Medicine. She earned her BS and PhD at Northwestern University, and then she conducted her residency in internal medicine and fellowship in hematology/oncology at Montefiore Medical Center. Dr. Chuy is a medical oncologist devoted to the care of patients with pancreatic cancer and other gastrointestinal malignancies, and she oversees the cancer center’s portfolio of clinical trials for patients with pancreatic cancer.
Although immunotherapeutic approaches have shown great promise in other cancer types, pancreatic tumors are known to be extremely immune-suppressive – meaning that the cancer cells and their surrounding complex tissue (stroma) actively block an immune response.
Drs. Gravekamp and Chuy strive to break through that immune-suppression by using an altered and weakened bacterium called “Listeria monocytogenes” (Listeria) that selectively infects tumor cells. The Listeria will be genetically modified to express proteins that the body should recognize due to childhood vaccines, like tetanus. The research team hypothesizes that the presence of the protein fragments that were introduced through a prior tetanus vaccine will activate specialized immune cells called memory T-cells, whose function is to seek out and kill cells that express proteins against which the body has been previously immunized (by exposure or vaccination).
In addition to activating memory T-cells, the Listeria bacteria themselves stimulate the production of toxins that could kill the cancer cells. Moreover, the treatment will be administered in combination with the chemotherapy gemcitabine, and Listeria is thought to further enhance cancer cell killing by eliminating one of the primary methods of resistance to gemcitabine.
Drs. Gravekamp and Chuy and their colleagues plan to further evaluate this Listeria and gemcitabine combination therapy in a genetically-engineered mouse model that adequately reflects human pancreatic cancer progression and metastatic spread. They will also verify whether the same memory T-cells can be reactivated in the blood of gemcitabine-treated pancreatic cancer patients through a booster with the tetanus toxoid vaccine. Ultimately, they expect that the combination therapy will be of great value as a safe and effective second-line therapy for metastatic pancreatic cancer patients who are resistant to gemcitabine alone.