- Allogeneic “off the shelf” chimeric antigen receptor-natural killer T cell (CAR-NKT) therapy platform could overcome significant challenges of current autologous CAR-T therapies
- Preclinical data indicate that engineered CAR-NKT cells do not mediate graft versus host disease (GvHD), unlike conventional CAR-T cells
- ANCHOR Phase 1 trial of CMD-502 off-the-shelf CAR-NKT therapy for relapsed/refractory (R/R) CD19 expressing B-cell malignancies expected to initiate in Q4 2019
HOUSTON and LONDON – May 1, 2019 – 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.”
1The data were part of an oral presentation “Development of an Allogeneic Universally Tolerated NKT Cell Platform for Off-the-Shelf Cancer Immunotherapy” given by Dr. Metelitsa.
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Notes to Editors
The American Society of Gene and Cell Therapy (ASGCT) Annual Meeting provides an international forum where the latest gene and cell therapy developments are presented and critically discussed. As the leading American conference focusing solely on gene and cell therapy, ASGCT’s annual meeting brings together more than 3,400 professionals including scientists, physicians, and patient advocates.
Find out more at: https://annualmeeting.asgct.org/am19
Media registration is open at: https://annualmeeting.asgct.org/forms/media_registration.php
About Cell Medica
Cell Medica is a clinical-stage biopharmaceutical company focused on transforming the treatment of solid and hematological cancers by developing next generation chimeric antigen receptor-natural killer T cell (CAR-NKT) therapies. Developing a portfolio of primarily allogeneic therapies, the company’s revolutionary platform engineers CARs on invariant NKT cells (iNKTs), a subset of T lymphocytes. A robust pipeline spanning both hematological and solid tumors is being created in partnership with Baylor College of Medicine and Texas Children’s Hospital. Headquartered in London, UK, the company also has facilities in Houston, US and Zurich, Switzerland.
About Baylor College of Medicine
Baylor College of Medicine (www.bcm.edu) in Houston is recognized as a premier academic health sciences center and is known for excellence in education, research and patient care. It is the only private medical school in the greater southwest and is ranked 16th among medical schools for research and 5th for primary care by U.S. News & World Report. Baylor is listed 21st among all U.S. medical schools for National Institutes of Health funding and number one in Texas. Located in the Texas Medical Center, Baylor has affiliations with seven teaching hospitals and jointly owns and operates Baylor St. Luke’s Medical Center, part of CHI St. Luke’s Health. Currently, Baylor trains more than 3,000 medical, graduate, nurse anesthesia, physician assistant and orthotics students, as well as residents and post-doctoral fellows. Follow Baylor College of Medicine on Facebook (http://www.facebook.com/BaylorCollegeOfMedicine) and Twitter (http://twitter.com/BCMHouston).