Research Institutes, Results

With CAR-T marketing looming, early study highlights potential of TCR engineering

With the first generation of CAR-Ts likely headed to a near-term approval for blood cancers, the clinical work on new adoptive TCR-engineered cell therapies that can work in solid tumors is underway.

Steven Rosenberg

This week, a research team led by the NIH’s Steven Rosenberg — whose work has been used as a basis of Kite Pharma’s pioneering CAR-T — rolled out early proof-of-concept data from a small human study using a CD4+ T cell adapted with a T cell receptor that zeroes in on MAGEA3, or melanoma-associated antigen A3.

Prepped with a lymphodepletion regimen and infused with a purified batch of cell therapy, the researchers treated 17 patients. One patient experienced a complete response which is ongoing at 29 months. Of 9 patients treated at the highest dose, three suffering from esophageal cancer, urothelial cancer, and osteosarcoma had partial responses.

Rosenberg and his team concluded that the PoC data was encouraging for this approach, a point which Kite executives were quick to endorse.

KITE-718 is already in the clinic, and it’s been designed along the same TCR engineering that Rosenberg was trying out at the NIH.

There are number of companies working on TCR therapies, including Adaptimmune $ADAP, which is closely allied with GlaxoSmithKline as the pharma giant looks at becoming much more active in the oncology field. While CAR-Ts have had a big impact on liquid cancers, solid tumors have remained a challenge, inspiring these next-gen approaches.

There are some key concerns about off-target toxicity here, underscored by two deaths four years ago in one of Adaptimmune’s TCR studies aimed at MAGEA3. They both died of heart failure, which was subsequently tied to an unexpected impact on cardiac muscle cells.

There were no signs of such toxicity in the NIH study, but you can bet that after the big safety issues that afflicted early CAR-T studies, it will be a major focus for all concerned.

“We are very excited by the results of this study conducted by our collaborators at the NCI, demonstrating the potential of TCR engineered T-cell therapy in common solid tumors,” said David Chang, Kite’s CMO. “The KITE-718 program is built upon this proof of concept study and incorporates Kite’s next generation T-cell manufacturing technology that is designed to enhance cell expansion and persistence. The findings from the NCI study will help inform us as we advance KITE-718 for the treatment of metastatic solid cancers, for which there is a great unmet medical need.”

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
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Atlas Venture Cambridge, MA

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