University of Minnesota Conducts Cutting-Edge Phase 1 Clinical Trial: Gene Therapy Applied to Solid Tumors

Oct 14, 2020 | Cancer, CRISPR/Cas9, Gastrointestinal Cancer, Investor Watch, News, Oncology, University of Minnesota

University of Minnesota Conducts Cutting-Edge Phase 1 Clinical Trial Gene Therapy Applied to Solid Tumors

The University of Minnesota now conducts a Phase 2 clinical trial for the treatment of metastatic gastrointestinal solid tumor cancer. Exclusively conducted at the M Health Fairview University of Minnesota Medical Center, the team employs cutting-edge CRISPR genetic engineering and now is enrolling patients. This treatment, made possible by a consortia of National Cancer Institute (NCI) and University of Minnesota investigators, were the first to use CRISPR for editing a intracellular checkpoint known as Cytokine-Induced SH2 protein (CISH) in a bid to turbo charge T cells’ fight against cancer in the human clinical environment. The implications are significant as, to date, gene therapies have mostly shown promise with hematological malignancies. Now the potential to target solid tumors raises significant opportunity to address major cancers such as breast cancer, gastrointestinal cancer and lung cancer. The background to this potentially valuable investigational therapeutic involves concerted challenges to the exclusive grant of intellectual property license from NCI to the sponsor—the somewhat mysterious Intima Bioscience. TrialSite shines a little more light on the subject.

The Challenge to Date

CAR-T and other cutting-edged cell therapies such as natural killer cells evidence real promise in liquid tumors but thus far they haven’t fared well targeting solid tumors. 

The Study Solution

University of Minnesota News informs readers with the introduction of CRISPR genetic engineering of neo-antigen enhanced Tumor Infiltrating Lymphocytes (TIL), in which the gene for the novel cancer checkpoint CISH was knocked out, there have been promising pre and peri-clinical data in solid tumors which the investigators now hope to translate into the human clinic.

What was Accomplished Thus Far?

A team including Principal Investigators Branden Moriarity, PhD, Beau Webber, PhD, and R. Scott Mclvor, PhD of the University of Minnesota Medical School and the Masonic Cancer Center collaborated with NCI’s Surgery Branch investigators to utilize CRISPR/Cas9 technology to delete a gene called CISH in human T cells.

The Breakthrough: Why Relevant?

The team suspects that CISH is involved with inhibiting T cells from identifying and terminating cancerous tumors and as it lives inside the cell the team didn’t have the means to actually stop or block it in the same way that other checkpoint therapies such as PD-1 work. Dr. Moriarity suggested, “Given the potential power of CISH to increase anti-cancer killing of solid tumors, we turned to CRISPR, Cas9 based genome engineering.”

The breakthrough: inactivate CISH at the genetic level and boost the ability of T cells known as tumor-infiltrating lymphocytes (TILs) to identify and actually kill these cancer cells. Dr. Webber chimed in, “With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells.”

The Clinical Trial

University of Minnesota’s Emil Lou, MD, PhD, FACP, Associate Professor, will lead the clinical trial that’s sponsored by Intima Bioscience. The clinical trial (NCT04426669) involves an investigation into the safety and efficacy of genetically-engineered, neoantigen-specific Tumor Infiltrating Lymphocytes (TIL) in which the intracellular immune checkpoint CISH has been inhibited using CRISPR gene editing for the treatment of Gastro-intestinal (GI) cancer.  

The study actually started in May during the COVID-19 pandemic but thanks to the dedication and resourcefulness of University of Minnesota team members, the trial has commenced and enrolling patients. Patients for this study have come from around the world.

How are the Patient-Specific CRISPR-engineered T Cells Produced?

For this study, these will be produced at the University of Minnesota’s Molecular and Cellular Therapeutics (MCT) facility. The MCT is one of only five such gene and cell therapy manufacturing centers in the country.

The Mysterious Sponsor

New York-based Intima Bioscience secured an exclusive license for the intellectual property underlying genetically-modified lymphocytes for cancer therapy. The unfolding of this deal involved some drama and mystery. As discussed below, a few activist groups teamed together to challenge the NCI’s award of exclusive license to this venture for public policy reasons. One of the challenges was that the company involved with the deal was sort of a mystery—at the time last year no website, no names associated with it except for an obscure investment group called Intima Capital, LLC in New York City. As it turns out, this small firm is run by a Boston-based physician named Modassir Choudhry. But the physician was able to secure the deal and he just recently organized a true company, again apparently associated with some controversy (see below); Campbell Murray joined as CEO just this month.

The IP Challenge

Owned by the NCI, in 2019 they published their intent to award an exclusive license via the Federal Register.

This was an important matter as a group of organizations challenged this grant of exclusive license for public policy reasons. Why? Existing gene therapies have been effective with hematological malignancies and given this technology’s ability to impact solid tumors have great implications for diseases such as breast cancer, gastrointestinal epithelial cancer and lung cancer. The various challengers were concerned this powerful capability developed with taxpayer funding should potentially be more open and accessible. To review the objection letter review here.    

About the Masonic Cancer Center, University of Minnesota

The Masonic Cancer Center, University of Minnesota, is the Twin Cities’ only Comprehensive Cancer Center, designated ‘Outstanding’ by the National Cancer Institute. As Minnesota’s Cancer Center, we have served the entire state for more than 25 years. Our researchers, educators, and care providers have worked to discover the causes, prevention, detection, and treatment of cancer and cancer-related diseases. Learn more at cancer.umn.edu.

About the University of Minnesota Medical School

The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. Learn how the University of Minnesota is innovating all aspects of medicine by visiting www.med.umn.edu.

Lead Research/Investigator

Emil Lou, MD, PhD, FACP, Associate Professor of Medicine at the Medical School in the Division of Hematology, Oncology and Transplantation and Medical Director of the Cancer Center’s Clinical Trials Office-Solid Tumor Unit

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