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Sunnybrook researchers engineer powerful human T cell expander for adoptive cell therapies

November 24, 2020

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A team of biochemists at Sunnybrook Research Institute (SRI) have engineered a dual-function protein termed T-CEP, that works as a soluble factor, enabling scientists to more efficiently and precisely expand in-culture specialized subsets of human immune cells needed for adoptive cell therapies aimed at treating cancer patients.

The design of T-CEP was recently published in JCI Insight.

“For adoptive cell therapy, scientists take either immune cells (T cells) from patients and modify them or develop them off the shelf, before infusing them back into the patient to eliminate specific cancer cells,” says Dr. Jean Gariépy, a senior scientist at SRI. “In both cases, these therapeutic cells need to be expanded ex-vivo first to generate enough of them to treat cancer patients. Current methods which use CD3 and CD28 pathway coactivation to expand T cells ex-vivo are costly and the resulting expanded human T cell subsets are often overly differentiated to the point where they aren’t as effective at doing their job in the patient.”

Esther Matus, a PhD student in the Gariépy Lab and the lead author on the paper, designed, constructed and tested T-CEP. Remarkably, this T cell expansion protein, activates, expands and differentiates human T cells ex vivo at concentrations in the femtomolar range. The patented protein was engineered in less than 18 months.

“We’ve also found that our compound yielded under-differentiated human T cell subsets, specifically non-terminally differentiated human T cells, in contrast with existing CD3/CD28 activation methods. We know that obtaining less differentiated CD8+ T cells after their expansion in culture is of interest for adoptive cell therapy as they have demonstrated superior antitumor immunity in vivo,” says Matus.

Dr. Gariépy underscores the importance of the discovery. “Our compound is simpler, cheaper and more effective than existing expanders. T-CEP may prove to be a game-changer for precision medicine based on emerging adoptive cell therapies.”

This work was supported by funding from the Canadian Institutes of Health Research (CIHR).

Read the publication in JCI Insight »