Hung Trinh: The use of chimeric antigen receptor (CAR)-T cells has demonstrated excellent results in B-lymphoid malignancies

Hung Trinh shared a post on LinkedIn:

“CAR-T cells targeting IL-1RAP produced in a closed semiautomatic system are ready for the first phase I clinical investigation in humans.

Purpose of the study
The use of chimeric antigen receptor (CAR)-T cells has demonstrated excellent results in B-lymphoid malignancies. The Advanced Therapy Medicinal Products (ATMP) status and good manufacturing practice (GMP) of CAR-T cells require particular conditions of production performed in a pharmaceutical establishment.

Our team developed a new medical drug candidate for acute myeloid leukemia (AML), a CAR targeting interleukin-1 receptor accessory protein (IL-1RAP) expressed by leukemia stem cells, which will need to be evaluated in a phase I-IIa clinical trial. During the preclinical development phase, we produced IL-1RAP CAR-T cells in a semi-automated closed system (CliniMACSࣨ Prodigy) using research grade lentiviral particles.

Patients and the methods
The purpose of this work was to validate our production process and to characterize our preclinical GMP-like medicinal product.
IL-1RAP CAR-T cells were produced from healthy donors in 9 days, either in an semi-automated closed system (with GMP-like compliant conditions) or according to another research protocols, which was used as a reference.

Results
Based on phenotypic, functional and metabolic analyses, we were able to show that the final product is ready for clinical use. Finally, in a xenograft AML murine model, we demonstrated that the IL-1RAP CAR-T cells generated in a GMP-like environment could eliminate tumor cells and increase overall survival.

Conclusion
We demonstrated that our IL-1RAP CAR-T cell preclinical GMP-like production process meets standard regulatory requirements in terms of CAR-T cell number, subpopulation phenotype and cytotoxic functionality. Our CAR-T cell production process was validated and can be used to produce medicinal IL-1RAP CAR-T cells for the first phase I clinical trial.”

CAR-T cells targeting IL-1RAP produced in a closed semiautomatic system are ready for the first phase I clinical investigation in humans

Authors: Clémentine Nicod, Mathieu Neto da Rocha, Walid Warda, Xavier Roussel, Rafik Haderbache, Evan Seffar , Rim Trad , Lucie Bouquet , Mathieu Goncalves, Léa Bosdure, Marie-Charlotte Laude, Mélanie Guiot, Christophe Ferrand and Marina Deschamps.

Source: Hung Tinh/LinkedIn

Hung Trinh is the Senior Director of Business Development at OBiO Tech. He previously served as Director of Process Development and Manufacturing Science and Technology at Vyriad and Associate Director of Downstream Process Development at Genezen. With experience in vaccine development, spanning both pre-clinical and clinical studies, Trinh has worked with various CDMOs focusing on lentiviral vector production and CAR-T cell manufacturing.