HSC-Engineered Off-The-Shelf iNKT Cell Therapy For Cancer

Tech ID: 30326 / UC Case 2018-594-0


UCLA researchers in the Department of Microbiology, Immunology, and Molecular Genetics, and the Department of Pathology & Laboratory Medicine have developed novel methods to produce invariant natural killer T (iNKT) cells from hematopoietic stem cells (HSCs) at high efficiency and yield for the development of off-the-shelf universal HSC-engineered iNKT cell therapy for cancer.


The success of using chimeric antigen receptor (CAR)-engineered adoptive T cell to target certain blood cancers have set the foundation for cell-based immunotherapy to become the new generation of cancer medicine.  However, most of the current protocols for cell-based therapy consist of autologous adoptive cell transfer, wherein immune cells collected from a patient are manufactured and used to treat this single patient.  This type of approach is costly, labor intensive, and difficult to deliver to all patients in need.  Thus, allogenic immune cellular products that can be manufactured at large scale and readily distributed to treat a broad range of cancer patients are in great demand.

Invariant natural killer T (iNKT) cells target multiple types of cancer independent of tumor antigen- and major histocompatibility complex (MHC)-restrictions, and they can deploy multiple mechanisms to attack tumor cells through direct killing and adjuvant effects.  Most importantly, they do not cause graft-versus-host disease (GvHD), making them attractive candidates for the development of universal off-the-shelf cellular therapy for cancer.  However, because of their extremely low numbers and high variabilities in humans, it is challenging to grow therapeutic numbers of iNKT cells from peripheral blood cells of allogenic human donors.


Researchers at UCLA have developed a novel method to generate iNKT cells from hematopoietic stem cells (HSCs) through iNKT T cell receptor gene engineering.  An artificial thymic organoid in vitro culture system further supports the differentiation of human HSCs into T cells at high efficiency and high yield.  Using this approach, G-CSF-mobilized CD34+ HSCs harvested from a single healthy donor can be used to produce 1012 scale of homogenous human iNKT cells of potent tumor killing capacity, which is equivalent to 1,000 to 10,000 doses of therapeutic cellular products.


  •  Production of universal off-the-shelf iNKT cells for cancer immunotherapy for patients with cancers that have been clinically indicated to be subject to iNKT cell regulation

         - Multiple types of solid tumors (melanoma, colon, lung, breast, head and neck cancer)

         - Blood cancers (leukemia, multiple myeloma, myelodysplastic syndromes)


  • iNKT cells are capable of attacking tumor cells via multiple mechanisms, independent of tumor antigen- and major MHC-restrictions
  • iNKT cells do not cause graft-versus-host disease, making it an ideal candidate for developing universal off-the-shelf cell therapy
  • The artificial thymic organoid in vitro culture system can reliably generate a homogenous population of iNKT cells in large quantities

State Of Development

The artificial thymic organoid in vitro culture system has been experimentally validated, and the produced HSC-iNKT cells have shown to mediate robust tumor killing capabilities in mouse model.

Patent Status

Patent Pending

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  • Yang, Lili

Other Information


invariant natural killer T cells, iNKT, hematopoietic stem cell, HSC, cell therapy, immunotherapy, cancer

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