The allogeneic natural killer (NK) cells expressing the anti-CD147 chimeric antigen receptor (CD147-CAR-NK) is a novel cellular immunotherapy developed by scientists at Rutgers University to treat relapsed or refractory hepatocellular carcinoma (HCC) and other solid tumors.
CD147 is a transmembrane glycoprotein highly expressed in HCC cells. Integrating the unique biology of NK cells and CAR-T cells produce a clinically superior immunotherapeutic strategy. Data from in vitro and in vivo efficacy studies support that CD147-CAR-NK is a less toxic, more effective, and inexpensive therapy than either standard chemotherapy or other immunomodulators.
|Drug Modality||Chimeric antigen receptor expressing natural killer (CAR-NK) cells|
|Mechanism of Action||The cytotoxic activity of NK cells activated by specific binding of the CAR to CD147|
|Patent||Preparing PCT patent applications (19 years of patent life, orphan drug exclusivity)|
Protheragen Inc. is actively seeking partnership for CD147-CAR-NK. Potential collaboration can be a strategic alliance, licensing, or marketing agreement.
We look forward to hearing from you.
|Introduction||CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or basigin, is a transmembrane glycoprotein with two immunoglobulin-like domains and is part of a family that includes embigin and neuroplastin. The protein portion of CD147 is 28 kDa, but its high glycosylation increases its molecular weight to 43-66 kDa. CD147 is frequently overexpressed in human cancers, and significantly contributes to malignant phenotypes. CD147 may trigger the production or release of MMPs in surrounding mesenchymal and tumor cells, thereby contributing to tumor invasion.|
|Approved Name||Basigin (Ok blood group)|
|Gene Type||Protein coding|
|Synonyms||EMMPRIN; CD147; EMPRIN|
|Gene Function||The protein encoded by this gene, basigin, is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. Multiple transcript variants encoding different isoforms have been found for this gene.|
|Pathway||Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds; respiratory electron transport; matrix metalloproteinases; degradation of the extracellular matrix; pyruvate metabolism and citric acid (TCA) cycle; adhesion; cell surface interactions at the vascular wall; ECM-receptor interaction; syndecan-1-mediated signaling events|
|Major Conditions||Hepatocellular carcinoma, pancreatic cancer, ovarian cancer, breast cancer, mucopolysaccharidosis, etc.|
NK cells are genetically engineered to express chimeric antigen receptors targeting CD147. The CAR of CD147-CAR-NK is the third generation CAR expressed by the SFG retroviral vector used in clinical trials. The CAR contains the single-chain variable fragment (scFv) of the anti-CD147 antibody, a human IgG1-CH2CH3 hinge region, the transmembrane domain of CD28, the intracellular domain of co-stimulatory CD28-4-1BB, and intracellular signaling domains of CD3ζ chain.
The scFv sequence has been optimized for targeting CD147 with high specificity. The intracellular domain also has been optimized for NK cell proliferation and persistence.
Fig. Schematic of CD147-CAR Construct
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth leading cause of cancer-related mortality in 2018 globally. The most prominent factors associated with HCC include chronic hepatitis B and C viral infection, chronic alcohol consumption, aflatoxin-B1-contaminated food, and virtually all cirrhosis-inducing conditions.
Treatment of HCC varies by the stage of the disease, a person’s likelihood to tolerate surgery, and availability of liver transplants. For patients with early-stage HCC, surgical resection, liver transplantation, or local ablation therapy are usually the solution, with a 5-year survival rate up to 75%. Transarterial chemoembolization is often considered for unresectable HCC without liver decompensation, and the 2-year survival rate was estimated to be 20–25%. In patients with far-advanced or terminal stage HCC, a dismal prognosis is anticipated and usually, supportive care is provided.
Due to the fast changes in the availability of cancer treatment selection over the past decades, novel therapeutics are expected to further prolong the long-term survival of HCC patients.
CD147-CAR-NK is NK cells modified to express chimeric antigen receptors targeting CD147, a transmembrane glycoprotein highly expressed in aggressive disease states, such as in HCC cells.
Specific binding of the anti-CD147 chimeric antigen receptor to CD147 on the tumor-cell surface triggers CAR activation, resulting in re-orientation of cytotoxic granules toward the immunological synapse formed between NK and target HCC cell, followed by the release of perforin and granzymes from cytotoxic granules into the synaptic cleft. Perforin and granzymes taken up by the target HCC cell then trigger apoptotic cell death.
Figure from Front. Immunol., 14 November 2019
Data from preclinical efficacy studies support the therapeutic potential of CD147-CAR-NK in patients with HCC and other solid tumors. An efficient NK cell expansion and manufacturing process was established, producing cells with superior purity and specificity.
CD147-CAR-NK is open for global licensing opportunities. The startup company with this proprietary technology is looking for investment and strategic partners to support CD147-CAR-NK development towards IND filing and early clinical trials.
Please feel free to contact us for data.
|Diane Hong Business Development Manager|