The currently marketed CAR-T therapies cannot discriminate between healthy and malignant B-cells says Xenetic Biosciences, which is buying a technology to enhance the safety and efficacy of such products.

The XCART technology platform, developed by the Scripps Research Institute in collaboration with the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, will be used by Xenetic Biosciences to develop cell-based therapeutics for the treatment of B-cell Non-Hodgkin lymphomas.

The two chimeric antigen receptor (CAR) T-cell products on the market – Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) – are approved to treat B-cell Non-Hodgkin lymphoma. But they target CD19 as the B-cell surface antigen, which has its drawbacks, Xenetic told us as CD19 is expressed on normal B-cells, not just malignant ones.

Image: iStock/Shidlovski

“Therefore, the currently marketed CAR-T therapies for B-cell lymphomas cannot discriminate between healthy and malignant B-cells. On the other hand, since each unique clonal B-cell line (whether healthy or malignant) expresses a unique B-cell receptor on its surface, the XCART platform can produce a CAR-T call that targets only malignant B-cell clones defined by a given BCR,” Xenetic said.

“The XCART technology platform was designed by its originators to utilize an established screening technique to identify peptide ligands that bind specifically to the unique B-cell receptor on the surface of an individual patient’s malignant tumor cells. The peptide is then inserted into the antigen-binding domain of a CAR, and a subsequent cell engineering process is used to modify the patient’s T cells into a CAR-T format which redirects the patient’s T-cells to attack the tumor.”

“Essentially, the XCART screening platform is the inverse of a typical CAR T screening protocol wherein libraries of highly specific domains are screened against a given target, in order to identify an suitable antigen-binding domain for the CAR construct. In the case of XCART screening, the target is itself an antibody domain, and hence highly specific by its nature. The XCART technology creates the possibility of personalized treatment of lymphomas utilizing a CAR with an antigen-binding domain that should only recognize, and only be recognized by, the unique BCR of a particular patient’s B-cell lymphoma.”

The firm is set to explore all available options to advance the XCART technology, it said. “While we have not yet determined a Phase I protocol, our initial internal programs will likely target Non-Hodgkin Lymphomas.”

Financial terms of the deal – expected to close in the first half of 2019 – have not been divulged, but Xenetic will acquire all outstanding shares of Hesperix, a newly-formed Swiss entity to which all XCART owners and inventors other than Scripps have assigned their rights to XCART, and will exclusively license Scripps’ rights in the technology, in exchange for an aggregate 7,500,000 shares of Xenetic common stock.