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“Off-the-shelf T cells” produced from the iPS cells
Recently, it has been shown that T lymphocytes can serve as effective therapeutic tools for cancer. In adoptive T cell therapy, T lymphocytes are collected from a patient’s peripheral blood, and after the expansion process, they are autologously administered back to the patient. However, such strategies using “autologous” T cells have the following issues:
- long preparatory period for transplant where it typically takes months to prepare patients for transplant procedures
- heterogeneity due to uneven quality of T cells derived from patients
The technology is targeted to overcome the above challenges associated with adoptive T cell therapy through the approach of a universal, off-the-shelf killer T cell medicine. The main target diseases are cancer and viral infections. This strategy of universal T cells leverages on induced pluripotent stem cells (iPSC), which exhibit low risk of host rejection, thereby allowing therapy options universally available to all patients.
The technology involves the large-scale production and subsequent cryopreservation of T cells. When needed, T cells will be thawed and administered to patients. Moreover, a mass production will make it possible for achieving cost efficiency. The technology provider hopes to provide cancer patients or patients having viral infections readily available access to T cell therapy.
The technology and its associated patents are currently licensed to a pharmaceutical company for the scope of use restricted to specific target antigens. The technology provider is seeking potential licensees for other target antigens.
Technology Features, Specifications and Advantages
The technology focuses on the following three methods (patented and patent-pending):
- T-iPSC method: iPSCs produced from T cells (T-iPSCs) inherit rearranged T cell receptor (TCR) genes, and thus all regenerated T cells from T-iPSCs express the same TCR. Based on this idea, the technology provider has previously succeeded in regenerating tumor antigen-specific CD8 T cells.
- TCR-iPSC method: To apply the above approach in allogeneic setting, the technology provider next developed a method in which non-T cell derived iPSCs are transduced with exogenous TCR genes (TCR-iPSC method). The technology provider recently published the data showing that the T cells produced by TCR-iPSC method are comparable to those produced by T-iPSC method. This method has so far been patented in EU, Australia, and Japan.
- The culture method to induce potent cytotoxic T lymphocytes from iPSCs: the technology provider developed a culture method by which CTLs expressing CD8ab can be generated. This method has been patented in EU.
- Application to cancer immunotherapy
Currently, the technology provider is developing a therapeutic strategy for acute myeloid leukemia targeting the WT1 antigen. The first clinical trial is planned to be conducted in 2024. Since WT1 antigen is widely shared with various types of solid tumors, this strategy can be broadly applied to various solid tumors. In parallel with this project, the technology provider is also developing a new strategy to use the regenerated T cells as platform cells in CAR-T cell therapy. This is in collaboration with a pharmaceutical company.
- Application to COVID-19
Many kinds of immunotherapies for the novel coronavirus infection COVID-19 are being developed all over the world: vaccination, antibody administration, recovered patient’s plasma administration etc. On the other hand, the current killer T cell medicine described herein is a novel strategy that differs from these existing strategies. Therefore, the success in development of this therapy will bring about a new modality against COVID-19 to humankind. The development of this strategy is performed in collaboration with another local university where clinical trials of Avigan on COVID-19 were conducted. Hence the current partnership scheme has been very competent in the development of treatment for COVID-19. In this collaborative research project, the technology provider firstly cloned T cell receptor gene that is specific to Corona virus, and produced anti-virus T cells by using the iPSC method. The technology provider aims to start a clinical trial within 2 to 3 years.
The killer T cells regenerated from iPSCs can be applied to any kinds of adoptive T cell therapy, including TCR-T and CAR-T cell therapies that target cancer or viral infections.
The technology presents the following benefits:
- Features of off-the-shelf and cryopreservation stockpiles allow readily available access to killer T cell medicine that leverages on iPSC technology
- Versatile in nature – amenable to different targets including cancer cells and virus