Advantage and Core Benefit
- CD37 is a promising target for CAR-T therapy against resistant B-cell malignancies with CD19 antigen target loss
- Overcoming problem on CD37-expressed T-cell fratricide
- CD37-CAR can be combined with CD19-CAR or other target CAR for divalent or trivalent CAR-T
Background and Technology
CAR-T have emerged as a novel form of treatment of patients with B-cell malignancies. In particular, CD19-CAR-T therapy has effected impressive clinical responses in B-cell malignancies. However, not all patients respond, and relapse with CD19 antigen loss has been observed in all patient subsets. To overcome this problem, many groups have been testing new target antigens, dual-targeting and trivalent CAR-T preventing the resistant tumor.
CD37 is a 4-passage transmembrane protein. Although its biologic function is incompletely understood, CD37 is involved in various different cellular processes of lymphocytes. CD37 is expressed mainly on mature B cells and with low levels of expression on T cells and other blood cells. In B-cell malignancies, CD37 is highly expressed in mature B-cell neoplasms. Therefore, CD37 represents a promising target for B-cell lymphoma, and recently has been validated as a druggable target, using antibody-drug conjugates in clinical trials of B-cell lymphoma. CD37-CAR-T therapy, however, is believed to have significant problem because CD37-CAR-T kills T-cells expressing CD37 itself. That is called fratricide. Some other groups reported CD37-CAR-T but there is no report that demonstrated enough therapeutic effect.
Here, we challenged to overcome this fratricide problem and developed a new CD37-CAR-T cell as a drug for B-cell malignancies.
- Our Structurally Optimized CD37-CAR-T can proliferate specifically in response to CD37 positive cancer cell-line stimulation without T-cell fratricide
- Our CD37-CAR-T reduced tumor cells and prolonged survival in mice
Seitaro Terakura (Nagoya University)
- Non-confidential additional information and meeting (or T/C) for further discussion
- Feasibility study under CDA, MTA, Option or Collaboration research
- Commercialization of CD37 CAR-T under Technology License to contribute cancer therapy
Product No.: CD-02829