Research Projects
We have created this section of our web site to inform our members of the status of Grants the Foundation is currently supporting with the grants we have issued this year. ECEF has established a Research Subcommittee of the Medical Advisory Committee to give us guidance in determining what Research Projects ECEF will support in the future.
We have awarded a Grant, in January 2022, of $50,000.00 to Memorial Sloan Kettering Cancer Center which has brought our overall Grant total to over $1,000,000 from inception of ECEF.
As a new approach we have asked our Research Committee Chairman to answer a few questions dealing with our research efforts and the role ECEF has played in these projects
What are the goals for the project we are supporting for this coming 2022?
The goals for this year are (a) to obtain FDA approval to initiate a CAR T-cell therapy study for esophageal cancer (EC) patients, (b) to publish our results of tumor immune studies from a trial in which EC patients received chemoimmunotherapy, c) publish the results of a prospective trial of biomarker investigation in EC patients, and (c) develop EC tumor tissue back for future studies.
With the help of ECEF support, over the years, we have developed strong data to develop CAR (chimeric antigen receptor) T-cell therapy for EC. CAR T-cell therapy involves genetically engineering patients’ own immune cells- T cells to recognize and kill cancer cells when given back to the patient. We have already translated CAR T-cell therapy to phase I and II clinical trials in patients with lung cancer and mesothelioma. In the current next-generation CAR construct, we incorporated checkpoint blockade as well to deliver two-in-one immunotherapies to patients with EC. We are currently conducting IND studies required for FDA approval to initiate a clinical trial exclusively for EC patients. This clinical trial is partially supported by the Department of Defense (DoD) award. We hope to rise enough funds to be able to complete the study.
We have investigated immune microenvironment in EC patients following chemoimmunotherapy. We hope to have a manuscript published with these results this year.
We are also developing a esophageal tumors tissue back to facilitate future studies of immune investigations.
What would you say are the long-term goals for the projects ECEF is supporting?
The long-term goal is to be able to investigate and incorporate immunotherapies in the treatment of EC patients. We hope to complete initial phase trials in next 3 years and if the results are successful, to be able to conduct to a definitive trial within 5 years.
Can tell us the role that ECEF has played in these projects?
ECEF funding provided us crucial support to be able to progress to current trials. With ECEF support over the past 10 years – a) we developed a EC clinicopathological database to be able to conduct investigations, b) developed biomarkers for EC prognostication and treatment, these studies are published acknowledging ECEF support, c) conducted a prospective clinical trial (n=200 patients) to investigate the biomarkers developed, a manuscript is in preparation, d) completed and published a clinical trial wherein, using a device we developed in the laboratory, we measured intraoperative oxygen saturation of gastric conduit in EC patients, and e) conducted CAR T-cell therapy preclinical investigations and are able to obtain DoD support to initiate a clinical trial for EC patients.
The actual explanation of the projects we are supporting with our grants is as follows:
Project 1: CAR T-cell immunotherapy for esophageal cancer
Description: With the support of the Esophageal Cancer Education Foundation (ECEF), we identified mesothelin as a cancer cell-surface antigen to redirect the body’s own immune cells—T cells—to target esophageal cancer. Our laboratory developed mesothelin-targeted chimeric antigen receptor (CAR) T cells and translated them in phase I and II clinical trials to patients with mesothelioma, lung cancer and breast cancer. Having reported that mesothelin is an effective target to treat patients with esophageal cancer, with the support of the ECEF, we applied for funding from the United States Department of Defense to conduct a phase I clinical trial for patients with esophageal cancer. I am pleased to report that we were awarded this funding, which will begin in the next quarter. In the meantime, with the support from the ECEF 2021 award, we have: a) established esophageal cancer cells with and without mesothelin expression, b) developed clinically relevant mouse models, and c) optimized the imaging modalities/protocols in these mice to monitor tumor burden. In addition, using the support from the ECEF, we tested CAR T cells against esophageal cancer cells in vitro and obtained promising results. These mouse models and results will play key roles in conducting investigational new drug (IND) studies to submit to the Food and Drug Administration (FDA) to obtain permission for and initiate the clinical trial for patients with esophageal cancer in 2022. The Department of Defense award can help us to investigate multiple CAR constructs to decide on which construct to move forward to the clinical trial.
Project 2: Immune microenvironment in esophageal cancer
Description: Our laboratory’s principal focus is investigating tumor immunology and immunotherapy. The tumor immune microenvironment in esophageal cancer is not well-studied. To advance immunotherapy, it is essential to understand the basic immune microenvironment of esophageal cancer. With this in mind, we developed a well-annotated clinicopathological database consisting of well-characterized tissue from a cohort of patients with esophageal cancer from an immunotherapy clinical trial led by Dr. Geoffrey Y. Ku. Our team has developed a similar database for patients with lung cancer (>2000 patients) and published more than 20 publications to date, which were published in notable journals such as the Journal of Clinical Oncology and the Journal of the National Cancer Institute. To date, we have updated the clinical database and identified patients who have proper tissue available. Using a novel technology called multispectral immune imaging, we quantified and characterized immune cell phenotypes on tumor slides. As a control, we obtained tissue from patients with esophageal cancer who received chemoradiation therapy but not immunotherapy, and assessed their tumors with multiplex immunoimaging. Our ongoing analyses will focus on a strategy to compare the tumoral and stromal immune microenvironment in esophageal tumors of patients who received immunotherapy with or without chemoradiation therapy. The results of this project can support design of the clinical trial in project 1
Including the $50,000 we gave as a grant to Memorial Sloan Kettering Cancer Center in January 2022; our total research project support is at $1.001.800.
Our goal for 2022 is to raise $75,000 that will bring us to the $1,076,800 grants from inception of ECEF.