Researchers at the University of Pennsylvania (Penn) are developing a new way for cancer-fighting CAR-T cells to overcome the resistance present in some types of B-cell driven cancers.

Although CAR-T treatments have proven effective against numerous cancer types, chronic lymphocytic leukemia (CLL) has so far proven difficult to treat.

But new research from researchers at Penn – who pioneered CAR-T technology – could provide a solution.

Penn researchers found that by inhibiting ‘bromodomain and extra terminal’ (BET) proteins, they could improve CAR-T cell function by fighting ‘T-cell exhaustion’ – a phenomenon that hinders genetically-engineered T-cells from fully fighting certain cancers.

It’s a significant finding, as many CLL patients undergo aggressive chemotherapy before receiving CAR-T treatments, and this chemotherapy process can leave many T cells exhausted.

Using a small-molecule drug called JQ1 to inhibit BET proteins during the cell engineering process, Penn researchers were able to lessen T-cell exhaustion and increase the production of CAR-T cells.

“Treating these ‘war weary’ T cells during the CAR T cell engineering process has the potential to boost responses, we’ve shown here,” senior author and assistant professor of microbiology at Penn Joseph A. Fraietta said.

“It’s setting the stage for a very promising set of next steps that rationalize further studies, including clinical trials, to prove this approach is safe and feasible.”

Prescient Therapeutics advances separate Penn technology

While the Penn research team have been fighting T-cell exhaustion, ASX-listed biotechnology company Prescient Therapeutics has partnered with the Peter MacCallum Cancer Centre to advance OmniCAR – a next generation CAR-T platform built using technology licensed from Penn.

OmniCAR is designed to give medical practitioners greater control over traditional CAR-T treatments – which genetically re-engineer a patients’ own immune system to identify and attack cancerous cells.

The platform is also designed to make treatment safer for patients and to be able to direct the CAR-T cells against a variety of cancer targets.

In July, immunogenicity testing on OmniCAR provided positive safety results.  The in-silico tests (meaning they were conducted by complex computer algorithms) found two binding components used in OmniCAR treatments, SpyTag and SpyCatcher, are unlikely to trigger adverse immune responses in patients.

Join Prescient Therapeutics CEO Steven Yatomi-Clarke for a special investor briefing next Wednesday, 25th August at 11am (AEST), where he will discuss the encouraging progress through clinical trials of Prescient’s foundational assets PTX-100 and PTX-200, provide an introduction into the amazing field of CAR-T, and how Prescient’s next gen CAR-T platform, OmniCAR, is seeking to take this burgeoning cancer field to the next level. Click here to book in.

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Sources:

• Fierce Biotech: Novartis-backed Penn study proposes boosting CAR-T responses in CLL by waking up ‘war weary’ T cells
• Penn Medicine: Existing Drug May Help Improve Responses to Cellular Therapies in Advanced Leukemias
• ASX: PTX announcement 5 July 2021
• PTX: Technology