CAR-NKT
We are developing a wide range of CAR-NKT cell products to treat different types of highly prevalent tumors. The CAR-NKT cell product candidates include both autologous (CMD-501) and allogeneic (CMD-502, CMD-503 and CMD-505) products.
iNKT cells or type 1 NKT cells are innate-like T lymphocytes that reside preferentially in tissues, including the bone marrow. They express a semi-invariant T cell receptor (TCR) that recognizes glycolipid antigens presented by the non-polymorphic MHC class I-like molecule CD1d. Evidence from pre-clinical studies suggest that iNKT cells do not mediate graft-versus-host-disease (GVHD) making them an ideal candidate for off-the-shelf CAR-therapy. In addition to this differentiated cellular biology, we have engineered the innovative CAR construct to:
- Secrete IL-15 to improve their activation, persistence and anti-tumor activity
- Down-regulate MCH class I and II to diminish their alloreactivity and improve persistence in allogeneic recipients

- Long time required for manufacturing
- Product-to-product variability due to patient factors
- Limited success in solid tumours
- Off-the-shelf therapies immediately available
- Large number of uniform doses manufactured from a single donor
- NKT cells naturally home to tissues
- NKT cells modulate immuno-suppressive cells
- CAR-T cells cause GvHD
- Uncertain persistence
- NKT cells do not mediate GvHD
- Fully functional TCR and no TCR gene editing required
- Engineered to secrete IL-15 to prolong persistence
- MHC knock down reduces immunogenicity
Unique platform for off-the-shelf cell products
- Express an invariant T cell receptor (TCR) that recognizes glycolipids presented by CD1d and does not mediate GvHD
- No TCR gene editing is required
Reside preferentially in tissues and home to tumor sites
- Presence of NKT cells in solid tumors correlates with favorable prognosis
Engage both tumor and immuno-suppressive myeloid cells
- Kills tumor cells through CAR engagement
- Kills or reprograms M2-macrophages and MDSCs through invariant TCR engagement
- Kills CD1d positive tumors (B cell/myeloid origin) through invariant TCR engagement
Homogeneously expanded and manufactured in high numbers
- Invariant TCR facilitates expansion in the presence of aGalCer


- T cells or NKT cells from a same human donor transfected with the identical CAR
- Injected into tumor-bearing hu-NSG mice; analysed after 4-5 weeks for xeno-GvHD
A. Heczey et al, Blood, 2014; 124:2824-33.
Engineered to secrete IL-15:
- Improves activation under hypoxic conditions
- Enhances persistence and anti tumor activity invivo
shRNAs to down-regulate class I and II MHC
- Reduces recognition by the patients’ T cells
- Maintaining low level MHC class I prevents elimination by the patient’s NK cells
- Decreased immunogenicity improves persistence
Future CAR-NKT cell constructs will include a humanized scFv
- Diminish antigenicity and improve persistence
- Generated through our proprietary PENTRA™ Body technology

- The image panels show luciferase-labeled NKT cells administered to tumor-bearing mice
- The bright red imaging indicates higher numbers of NKT cells, which demonstrates stronger expansion and persistence
- The CAR-NKT cells engineered to express IL-15 show the highest expansion and persistence


We are developing an off-the-shelf CD19 targeted allogeneic CAR-NKT product for the treatment of relapsed, refractory CD19-positive malignancy.
CMD-502 CAR-NKT Therapy |
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CD19 Biology and Tumor Expression |
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Unmet Medical Need |
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Clinical Development Plan |
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We are developing a GD2-CAR NKT autologous product (CMD-501) for the treatment of neuroblastoma and small cell lung cancer. A first-in-human study is underway at Baylor College of Medicine (BCM) at Texas Children’s Hospital in Houston, TX
CMD-501 CAR-NKT Therapy |
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GD2 Biology and Tumor Expression |
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Unmet Medical Need |
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Clinical Development Plan |
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Our goal is to expand the off-the-shelf allogeneic CAR NKT platform to treat a wide range of tumor types including both solid and liquid tumors. These includes programs to CAR-NKT cell products to treat liver cancer (CMD-503), and multiple myeloma (CMD-505). All these programs are currently in pre-clinical development
Product Name | Target Tumors | Target Antigen | Upcoming Milestone |
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CMD-503 | Liver cancer, lung cancer, gastric cancer & others | GPC3 | Preclinical POC 2H 2019 |
CMD-505 | Multiple myeloma | BCMA | Preclinical POC 2H 2020 |