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Research Projects

What was achieved with ECEF funding support in the year 2023?

Memorial Sloan Kettering Cancer center is pleased to report the following accomplishments from 2023 with support from ECEF:

  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 been published in the prestigious Annals of Surgery journal (PMCID: PMC10593105). This publication was published on November 1, 2023. Link to the manuscript –
  2. Tumor immune studies from a prospective trial, in which patients with esophageal cancer (EC) received chemoimmunotherapy, have been published in the prestigious Annals of Surgery journal (PMID: 36762546). This publication was published on September 1, 2023. Link to the manuscript –
  3. We have initiated tumor immune microenvironment studies using the tissue microarray (TMA) of EC tissue, along with adjacent normal tissue that we methodically constructed in 2023. We are using phenocycler, a new technology, to simultaneously investigate scores of markers with spatial localization and colocalization; this state-of-the-art technology is the first in Memorial Sloan Kettering Cancer Center (MSK).
  4. We have completed chimeric antigen receptor (CAR) T-cell investigational new drug (IND) studies, which are required for Food and Drug Administration (FDA) approval to initiate the clinical trial. Our data and completed clinical trial protocol is going through reviews at MSK. We hope to initiate the trial in Q3 of 2024. ECEF support was critical for the generation of
    preclinical data.

What are the goals for the project we are supporting for this coming 2024?

The goals for 2024 are: (a) to initiate the CAR T-cell study for patients with peritoneal carcinomatosis from esophagogastric cancers, (b) to investigate pre- and post-treatment tumor and serum samples from patients with esophagogastric cancers collected prospectively in a conclusive clinical trial, and (c) to continue tumor immune microenvironment studies using esophageal cancer TMA. 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, triple-negative breast 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 have completed 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 applied for additional funds are awaiting the peer-review outcome.

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 as a near-term goal, and if the results are successful, to conduct a definitive trial as a long-term goal.

Can you 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, (f) methodically constructed tissue microarrays from EC and peritumoral normal esophagus, (g) conducted immune studies as a correlative to clinical trials that have now been published, and (h) conducted CAR T-cell therapy preclinical investigations required 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 patients with EC

Description: With the support of the ECEF, we identified mesothelin as a cancer cell-surface antigen to redirect the body’s own immune cells—T cells—to target EC. Our laboratory developed mesothelin-targeted 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 EC, with the support of the ECEF, we applied for funding from the DoD to conduct a phase I clinical trial for patients with EC. I am pleased to report that we were awarded this funding. With the support from the ECEF award, we have: (a) established esophageal cancer cells with and without mesothelin expression, (b) developed clinically relevant mouse models, most importantly aggressive peritoneal carcinomatosis models, and (c) optimized the imaging modalities/protocols in these mice to monitor tumor burden. In addition, using the support from the ECEF, we completed testing CAR T cells against EC cells both in vitro and in vivo with promising results to proceed to a clinical trial.

Project 2: Immune microenvironment in EC

Description: Our laboratory’s principal focus is investigating tumor immunology and immunotherapy. The tumor immune microenvironment in EC is not well-studied. To advance immunotherapy, it is essential to understand the basic immune microenvironment of EC. With this in mind, we developed a well-annotated clinicopathological database consisting of well- characterized tissue from a cohort of patients with EC from an immunotherapy clinical trial led by Dr. Geoffrey Y. Ku. To date, we have completed analysis of tumor biopsies obtained in two trials; in one of the trials, we compared the tumoral and stromal immune microenvironment in esophageal tumors of patients who received immunotherapy with or without chemoradiation therapy. We now have completed, again with ECEF support, a tissue microarray using post-treatment EC and peritumoral normal esophagus. We will continue analysis of tumor immune microenvironment in this TMA.

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