MB-105
MB-105 is a CD5 CAR T cell technology. The asset developed at Baylor College of Medicine, is currently in the clinic for the treatment of T-cell lymphoma (TCL), which represents 15% of all non-Hodgkin lymphomas.
Problem
T-Cell Lymphoma
Although targeted and cellular immunotherapies have improved the management of B-cell leukemia and lymphoma, patients with treatment-resistant or recurrent T-cell cancers face limited options. The current standard of care relies on chemotherapy and hematopoietic stem cell transplants, with limited targeted therapies available due to shared targets between normal and malignant T- cells. Chemotherapy refractory T-cell malignancies face an extremely poor prognosis, with typically a less than 20% 3-year survival.
Challenges
Challenging Targets for T Cell Malignancies
The main challenge in treating T-cell lymphoma or leukemia is the potential for on-target off-tumor activity, leading to undesirable side effects and severe immunodeficiency. A limitation that is faced also for CAR T cell therapy. The challenge remains due to the shared expression of targetable antigens between the malignant and normal T-cells.
CD5 as a Target
Our Solution
MB-105
March Biosciences’ lead asset, MB-105, selectively targets CD5, a widely expressed antigen both in normal and malignant T- cells. Leveraging our proprietary manufacturing processes combined with an optimized CAR design, we are able to overcome key challenges for CAR T cell therapy.
- On-target toxicities against normal T-cells : The specific engineering of MB-105 CAR enables preservation of normal T cells, while maintaining cytotoxicity against CD5+ tumor cells, avoiding risk of severe immunodeficiency
- Fratricide during CAR T-cell production: CAR T-cell to T-cell killing creates manufacturing production challenges. Our optimized CD5 CAR design achieves self- targeting resistance due to the rapid degradation of CD5 protein triggered by the CAR binding within T-cells.
- Terminal T-cell differentiation: CAR T-cell expansion promotes early terminal T-cell differentiation, resulting in potent but short-lived effector cells incapable of driving patient responses. In our technology, the reduced duration of CD5 CAR T-cell expansion post-transduction combined with the addition of pharmacological inhibitors, result in highly potent, minimally differentiated T-cell subsets with higher persistence and superior anti-tumor activity.
Publications
November 13, 2019
October 27, 2017
August 20, 2015
March 5, 2019
Ongoing trial
Autologous CD5 CAR T, developed at Baylor College of Medicine, is currently being evaluated in a Phase 1 clinical trial (NCT03081910) for T-cell lymphoma and T-cell acute lymphoblastic leukemia (TCL and T-ALL). Initial results have revealed promising signals of safety and efficacy for these patients, who otherwise have limited treatment options. Enrollment for this trial is ongoing.
Clinical Trial Identifier: NCT03081910