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Research Projects

What was achieved with ECEF funding support in the year 2022?

Our prospective clinical trial evaluating the biomarker in a serial fashion (tissue – from diagnosis and following resection, and peripheral blood – at diagnosis, during induction therapy, pre- and post-esophagectomy for up to 2 years) is now accepted for publication in the prestigious ‘Annals of Surgery’ journal. We expect the publication to be online within a month.

  1. Our prospective clinical trial that evaluated the biomarker in a serial fashion (in tissue from diagnosis and following resection, and peripheral blood at diagnosis, during induction therapy, and pre- and post-esophagectomy for up to 2 years) has now been accepted for publication in the prestigious Annals of Surgery journal. This publication was published
    online ahead of print on April 27, 2023. Link to the manuscript:
  2. Tumor immune studies from a prospective trial, in which patients with esophageal cancer (EC) received chemoimmunotherapy, have now been published in the prestigious Annals of Surgery journal (PMID: 36762546). This publication was published online ahead of print on February 10, 2023. Link to the manuscript:
  3. We completed phase I of constructing a tissue microarray (TMA) of EC tissue along with adjacent normal tissue.
  4. We completed 70% of chimeric antigen receptor (CAR) T-cell investigational new drug (IND) studies required for Food and Drug Administration (FDA) approval of initiating the
    clinical trial.

What are the goals for the project we are supporting in 2023?

The goals for 2023 are: (a) to complete part two of the TMA from EC tissue, (b) to complete in vivo studies to submit an IND application to the FDA, and (c) to submit the clinical trial protocol for IRB approval.

With the help of ECEF support, over the years, we have developed strong data to develop CAR T-cell therapy for patients with 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 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 patients with EC. This clinical trial is partially supported by a United States Department of Defense (DoD) award. We hope to raise enough funds to be able to complete the study.

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 patients with EC. We hope to complete initial-phase trials in the next 3 years, and if the results are successful, to conduct a definitive trial within the next 5 years.

Can tell us the role that ECEF has played in these projects?

Funding support from the ECEF supported us in completing two trials, of which the results have been peer-reviewed and published in high-impact journals, and progressing to future immunotherapy trials. With ECEF funding support, over the past 10 years, we have: (a) 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, (d) completed and published immune marker studies from a prospective trial, (e) completed and published a clinical trial wherein, using a device we developed in the laboratory, we measured intraoperative oxygen saturation of gastric conduit in patients with EC, and (f) conducted CAR T-cell therapy preclinical investigations and are now able to obtain DoD support to initiate a clinical trial for patients with EC.

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 2023. 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.

Based on our 2022 Audited Financial Statements results we will contribute $50,000 in support of the research projects mentioned above. This will bring our contributions to our research project account to $1,051,800 from the inception of ECEF. Our Administrative Expense for 2022 was only $5,064.

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