For the first time, four therapeutic genes have been inserted and one ‘unwanted’ gene removed from the DNA of preclinical models in a single intervention
These results come from a preclinical study conducted by the Cell Engineering team at Integra Therapeutics using the FiCAT gene-writing platform.
The Cell Engineering team at Integra Therapeutics has conducted a preclinical trial demonstrating the FiCAT platform's ability to simultaneously insert up to four genes in a therapeutic payload into a defined, safe location in the genome, while deactivating an unwanted gene—all in a single step.
These results are significant because current CAR-T cell therapy manufacturing typically requires multiple steps to introduce each genetic modification, increasing complexity, time, and cost, and limiting the amount of genetic information incorporated into the final product. The level of precision and multiplexing achieved with FiCAT in a single intervention has not previously been demonstrated.
The new preclinical data have been selected for an oral presentation at the American Society for Gene and Cell Therapy (ASGCT) Annual Meeting, held May 11–15 in Boston, Massachusetts.
Currently, retroviral and lentiviral vectors (LVVs) are the standard for manufacturing CAR-T cell therapies and are used in all approved products. In a head-to-head comparison—the most rigorous method for evaluating new technologies—T cells modified with FiCAT matched or outperformed LVVs in key performance indicators, including cell viability, tumor-killing ability, and genotoxicity associated with integration. Unlike LVVs, which insert genetic material randomly into the genome— posing risks such as oncogene activation or variable expression—FiCAT inserts genetic payloads into one specific predetermined safe site.
“We are very encouraged by the results of this preclinical validation, which position our FiCAT platform at the forefront of next-generation CAR-T cell therapies—safer, more capable, and scalable—for the treatment of autoimmune and oncological diseases that currently lack therapeutic alternatives. However, clinical validation will be required,” said Avencia Sánchez-Mejías, PhD, CEO and Co-Founder of Integra Therapeutics.
According to Margot Pont, PhD, VP Translational Development at Integra Therapeutics, “The application of FiCAT in primary T cells opens new possibilities for designing next-generation CAR-T cells, as it removes the size limitations of the current gold standard, with increased safety. The data presented at ASGCT are highly relevant, but we are committed to continuing to generate additional data needed for regulators, investors, and the pharmaceutical industry to support the adoption of this new platform as an alternative to the current standard.”
The company will soon complete the submission of a manuscript for publication in a high-impact scientific journal.