Investment in Immunotherapy Spurs Growth

The recruitment of world-class talent and investment in new technology position Cleveland as a leader in immunotherapy, the future of cancer care. Cleveland’s immunotherapy hubs are undergoing significant growth. Cleveland Clinic and MetroHealth Medical Center are developing new programs led by new top recruits, and University Hospitals (UH) is building a new facility funded by a large philanthropic donation. At the hub of all activity stands Case Western Reserve University (CWRU), serving as the longstanding expert with the infrastructure to ensure success.

The Case Comprehensive Cancer Center and the National Center for Regenerative Medicine (NCRM) at CWRU are home to a state-of-the-art Good Manufacturing Practice (GMP)-compliant cellular therapy manufacturing facility – one of few in academic institutions in the United States. The facility, led by Lan Zhou, MD, PhD, Scientific Director, and Jane Reese, MBA, Operations Director, has a reputation as one of the largest and best-run cell therapy facilities in the country. It is also the perfect setting to engineer the next generation of CAR-T cells faster and for less cost.

Cleveland Clinic Launches New Immunotherapy Center

Last year immuno-oncology and cancer genomics expert Timothy Chan, MD, PhD, was brought to Cleveland to lead the newly established Center for Immunotherapy and Precision Immuno-Oncology at Cleveland Clinic. He also co-directs the NCRM.

His decision to move to Cleveland from Memorial Sloan Kettering Cancer Center was driven by the exciting potential to build something special with CWRU and Cleveland Clinic. “Here, I have the opportunity to practice the lessons we learned and do things more efficiently, speeding up the translation of therapeutics to patients,” he says.

Chan has an ambitious vision for Cleveland Clinic’s immunotherapy program, including experimental therapeutics, early phase trials and resource development, and recruiting for basic research. “We are creating a tight network of people with complementary expertise, which is critical to making things more efficient and more innovative.”

Plans are in the works to expand usage of CWRU’s cell therapy facility. Ideally, says Chan, the program will look at solid and liquid tumors in terms of new clinical trials and alterations using CRISPR to adjust T cells and T cell constructs. This will allow parties to penetrate solid tumors better and overcome microenvironmental barriers. “I am excited to recruit people to make full use of that facility,” says Chan. “There’s a tremendous amount of potential.”

Resources are being built to capture patient-level genomic data and aid precision oncology. A cBioPortal user interface will allow clinicians and researchers to report mutation status. A new comprehensive clinical and genomic database is being built to capture all patients and sequence them as part of standard-of-care. Information can be used to answer research questions across the Cancer Center and allow clinicians to make informed decisions.

Adding to available resources to support cell therapy, the recently announced Immunomonitoring facility is a Case Comprehensive Cancer Center-wide initiative led by Marcela Diaz, PhD, and Jennifer Ko, MD, PhD. The facility will offer flow and biobanking, and immunomonitoring heavy on sequencing. A Discovery lab has been established to make large-scale technologies easily accessible to the Cancer Center, including single cell sequencing, spatial transcriptomics, TCR sequencing, HLA typing and single cell proteomics.

With the recent JobsOhio investment in cancer research at Cleveland Clinic, Chan says they are planning a buildout of a GMP vector facility in conjunction with the NCRM.

MetroHealth Cultivates New Immunotherapy Program

Across town at MetroHealth Medical Center, William Tse, MD, is building an immunotherapy program from the ground up. Tse is a bone marrow transplant physician with connections in research and industry technology developed from leadership roles throughout the years. Cleveland is a big biotech town with a “lot of soil to cultivate” and endless opportunities, says Tse, Director of Hematology and Oncology. “We are excited to be a part of it.”

Tse started his career at CWRU and left over a decade ago to grow his career, keeping in close contact with colleagues at the Case Comprehensive Cancer Center and the NCRM. Tse is astounded by the Cancer Center’s growth and success under Director Stan Gerson, MD. “The clinical trials are here. The faculty are amazing. Everything is streamlined and much stronger than when I left,” says Tse.

Tse and his team have plans in place to use the CWRU facility to produce CAR-T cells for a new investigational drug they are preparing to submit to the U.S. Food and Drug Administration.

MetroHealth is focused on increasing therapeutic clinical trial enrollment, especially in underserved populations. Signifi cant resources have been invested into immunotherapy, cancer program and clinical trials, including constructing a state-of-the-art GMP viral vector facility, recruiting top-notch NIH-funded scientists and improving clinical trial staff-to-patient ratios. The changes allow MetroHealth to operate and access the cutting-edge immunotherapy trials not available to them previously.

This is especially important because MetroHealth serves a particularly underserved population. The MetroHealth System is ensuring these patients have access to state-of-the-art cancer treatments available through the Cancer Center. MetroHealth is also expanding clinical trial enrollment beyond the main campus. For the first time, it offers therapeutic immunotherapy clinical trials to patients at community sites, closing the gap to access to care.

University Hospitals Secures Funding to Expand Immunotherapy Space

While its competitors are building new programs, UH is expanding its current booming immunotherapy space. UH Seidman Cancer Center received a $10 million gift to establish the Wesley Center for Immunotherapy at UH Seidman Cancer Center. University Hospitals will expand its current facility housed in the Wolstein Research Building in conjunction with the NCRM.

“We are tremendously expanding, with about 3,600 additional square feet of lab space, which will be used to create novel cell therapies and treatments for our patients,” says Ted Teknos, MD, President and Chief Scientific Officer of UH Seidman Cancer Center. “The new space will include three new clean rooms, doubling our capability for providing natural killer cell and other genetically modifi ed cell therapies for our patients.”

University Hospitals has 61 immunotherapy trials open, including 17 immunotherapy-centered trials originating from the cell therapy facility, generating CART, NK cell and other cell-based therapies.Cells for treatment are produced in eight days as opposed to 12-30 days from commercially available CAR-T trials.

“Manufacturing CAR-T cells on-site allows our physicians to deliver therapy in a timely manner and to more patients than would otherwise be possible,” says Teknos.

Results to date for patients have been quite promising.

“Of the 22 patients who have completed immunotherapy trials by receiving UH-generated CAR-T cells, there’s been an overall response rate of 85% and a 70% rate of complete remission,” Teknos says.

Beyond hematologic malignancies, UH Seidman Cancer Center oncologists are also exploring CAR T-cell therapies to attack solid tumors, specifically targeting the protein mesothelin. Pre-clinical work is underway, with the goal of offering a CAR-T clinical trial for pancreatic, ovarian, lung, and head and neck cancer patients within a year.

Future of Immunotherapy

To stay ahead of the curve, Tse advises Cleveland Clinic to jump beyond current immunotherapy, which is mostly focused on CD19, or beyond hematopoietic malignancy to develop for solid cancers. The Tse group is developing CAR-T cells that incorporate immunomodulation components, which should cut down patient relapse that is more common in CD19 CAR-T therapy.

Chan agrees there are many areas to expand current immunotherapy beyond T cells. NK cells are one option, which are already done here. There is also interest in T regulatory cells, including how to control them, and shut down autoimmunity and inflammatory disorders. Another area of interest is mesenchymal stem cells that can be altered and designed to do certain things better, such as secrete certain cytokines or behave a certain way.

“That’s where the cell therapy field may be headed,” says Chan. “What’s common to all this is a need for it to have a very robust manufacturing operation. We have the potential for all that here and more.”