Cell Medica, a leader in next-generation cellular immunotherapies for the treatment of cancer, today announced that collaborators from Baylor College of Medicine and Texas Children’s Hospital presented the latest preclinical data generated as part of the development program for CMD-502, an off-the-shelf CAR-NKT therapy candidate for R/R CD19 expressing B-cell malignancies, at the 22nd Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) in Washington, D.C.1
One of the challenges with allogeneic therapies is that infusing a patient with donor-derived lymphocytes can induce GvHD, a potentially life-threatening condition in which the infused cells recognize the patient’s tissues as foreign. The NKT cells used in Cell Medica’s CAR-NKT platform have an invariant T cell receptor (iTCR) that does not distinguish between self- and non-self tissues, making them unlikely to induce GvHD when given to another person. Preclinical data generated by the team at Baylor indicate that human CAR-NKT cells do not induce GvHD in mice, whereas CAR-T cells from the same human donor cause severe GvHD.
The CMD-502 off-the-shelf CAR-NKT cells target CD19 and are also engineered to secrete IL-15, to prolong persistence and enhance anti-tumor activity. In addition, the CAR-NKT cells express short hairpin RNA (shRNA) designed to downregulate HLA class-I and class-II expression, which may minimize rejection by the patient’s immune system and further enhance persistence. The CAR, IL-15 and shRNAs are effectively expressed in NKT cells via a single retroviral vector, allowing for one-hit generation of off-the-shelf CAR-NKT cells. In contrast to off-the-shelf CAR therapy with conventional alpha-beta T cells, gene editing to remove the TCR to prevent GvHD is not required for off-the-shelf CAR-NKT therapy.
Dr. Leonid Metelitsa, Professor of Pediatrics, Hematology-Oncology, Baylor College of Medicine and Co-Director, Neuroblastoma Program, Texas Children’s Cancer Center added: “We are excited about the potential of engineered off-the-shelf CAR-NKT cells. We believe these cells could be ideally suited for off-the-shelf CAR therapy, due to a combination of their potent tumor cell killing ability, increased persistence, reduced allogenicity, and the lack of mediation of GvHD.”
Chris Nowers, Cell Medica’s CEO, said: “The allogeneic approach holds huge promise and an opportunity to unlock the potential of CAR therapy for large patient populations in need. The fact that it will be logistically simpler, less expensive and quicker to manufacture than patient-specific autologous products could facilitate the broader adoption of CAR therapy. These new preclinical data further support our previous findings and bring us closer to the clinic, where we hope to establish the potential of our innovative CAR-NKT platform in an off-the-shelf setting.”