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CAR-T cell therapy

CAR-T cells are manufactured by introducing an artificial gene called a chimeric antigen receptor (CAR) into a type of white blood cell called T cells, which are taken from the patient's blood. The CAR has the ability to detect cancer cells with high sensitivity and to mount a strong attack against them. CAR-T cell therapy is a treatment in which CAR-T cells are expanded in culture for one to two weeks and then administered to the patient. CAR-T cells transfected with the CAR gene recognize and attack the cancer cells that express the target cancer antigen.


Development history and current status of CAR-T cell therapy

CAR-T cell therapy has been developed as a novel therapy for hematological cancers. Most notably, CAR-T cell therapy targeting the CD19 antigen, which is highly expressed in B-cell leukemia/lymphoma, and the BCMA antigen, which is highly expressed in myeloma, has proven effective in clinical trials. As a result, the first CD19 CAR-T cell therapy was approved for these hematological cancers by the US FDA in 2017, the EMA in 2018, and the Japanese authorities in March 2019.

CAR-T cell therapy has been demonstrated to be effective in treatment of hematological cancers; however, it has not been successfully applied to solid tumors. Despite efforts by academic institutions and pharmaceutical companies in many countries to develop CAR-T cell therapies targeting solid tumors, none has been approved to date. One of the known reasons for the difficulty of developing CAR-T for solid tumors is that these tumors differ from blood cancers, as shown in the image below. The delivery of CAR-T cells to localized areas of solid tumors and the heterogeneity of solid tumors (tumor heterogeneity) have been challenges.


Noile-Immune Biotech’s approach

Development of next-generation CAR-T cell technology that is effective for solid tumors is highly sought after all over the world. Our “Proliferation-Inducing and Migration-Enhancing (PRIME)” technology features improved local trafficking of CAR-T cells and other immune cells into solid tumors, which has previously been a challenge. It is also designed to address tumor heterogeneity by activating the host immune system and inducing immune responses to various cancer antigens. With PRIME technology, we aim to develop CAR-T cell therapy that is truly effective for solid tumors. We are advancing research and development to achieve our goal of quickly providing safe and effective therapies to all cancer patients.

PRIME CAR-T cell therapy

The diagram below illustrates the differences between conventional CAR-T cell therapy and our PRIME CAR-T cell therapy.

When conventional CAR-T cell therapy is applied, it is difficult to deliver enough CAR-T cells to solid tumor tissues. In addition, although CAR-T cells can selectively attack cancer cells expressing specific cancer antigens, they cannot attack cancer cells that do not express cancer antigens.



In PRIME CAR-T cell therapy, CAR-T cells are genetically modified to simultaneously produce interleukin-7 (IL-7) and CCL19. IL-7 and CCL19 are immune regulators produced by fibroblastic reticular cells in the T-cell zone of the lymph nodes, where T cells and dendritic cells accumulate. These immune regulators are thought to play crucial roles in the formation of the T-cell zone. IL-7 is known to promote the growth and survival of T cells, and CCL19 is known to enhance the migration of T cells and dendritic cells. PRIME technology was developed to create an environment in which CAR-T cells and the body’s immune cells can easily attack cancer cells by forming a structure at the cancer site that resembles the T-cell zone formed in the body's lymph nodes, as described above.



In mouse models with solid tumors, intravenously administered PRIME CAR-T cells accumulated more efficiently in tumor tissues than conventional CAR-T cells and demonstrated highly potent anti-tumor therapeutic activity (Nature Biotechnology, 36(4):346-351, 2018)


Moreover, in mice that once rejected a solid tumor after treatment with the PRIME CAR-T cell method, long-term prevention of recurrence was demonstrated not only against the CAR target-positive tumor cells, but also against the parental tumor cells lacking the CAR target antigen (see the above publication).

List of references related to PRIME technology

Please check the video for an overview of PRIME CAR-T cell therapy