Clinical-stage biopharmaceutical company, Autolus, has announced the publication of pre-clinical data of a novel, dual-targeted, proliferating-inducing ligand (APRIL) chimeric antigen receptor (CAR) for the treatment of multiple myeloma.
multiple myeloma
The data, published in the journal of the American Society of Hematology, demonstrate that in multiple myeloma patient samples variable and typically low levels of B-cell maturation antigen (BCMA) or calcium modulator and cyclophilin ligand interactor (TACI) are expressed. Using CAR T-cells, with a modified form of human APRIL, the researchers found that both BCMA and RACI were recognised. The modified CAR T-cells were shown to effectively kill in vitro primary multiple myeloma cells and cell lines expressing a physiological range of either BCMA or TACI. Furthermore, this dual targeting approach was found to suppress persistent disease in animal models in vivo, even in the event of BCMA downregulation or loss.
Dr Jesus G. Berdeja, director of Myeloma Research & Senior Investigator, Hematologic Malignancies, Sarah Cannon Research Institute commented: “Emerging evidence shows that the level of available antigen on the surface of cancer cells may be an important factor in determining the efficacy of CAR T-cells. Treatment of multiple myeloma with its low antigen expression may benefit from a dual targeting approach, potentially impacting both initial response and reducing relapse.”
“This publication illustrates an example of our approach to address defence mechanisms used by cancers cells to evade CAR-T treatment,” added Dr Christian Itin, CEO of Autolus. “Variable antigen expression and antigen loss under CAR-T treatments have been reported for multiple myeloma and B cell malignancies. Dual targeting CAR-T approaches may maximise initial treatment effect and minimise the risk of relapse.”
AUTO2, an APRIL CAR-T therapy is currently under clinical investigation in the APRIL study, a single-arm, open-label, multi-centre, phase I/II study evaluating the safety and clinical activity in patients with relapsed or refractory multiple myeloma.