Development of personalized immune therapy system

Project Leader	Atsushi MURAGUCHI Professor, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
U R L	http://www.med.u-toyama.ac.jp/immuno/index.html
Participating Research Organizations   Toyama University, Toyama Prefectural Institute for Pharmaceutical Research, Toyama Industrial Technology Center, SC World Inc., National Institutes of Health

In our body, antigen-specific lymphocytes play a vital role on fighting against virus and cancer. Isolation and amplification of each antigen-specific lymphocyte may contribute on infectious disease or cancer therapy. In this project, we try to establish a system in which we can detect and isolate antigen-specific TCR (T cell receptor) genes, followed by generating functional TCR and T lymphocytes. Furthermore, we unfold a new system for isolating antigen-specific B lymphocytes and rapid production of human monoclonal antibodies. We will recombine antibody therapy and cellular therapy, establishing “an personalized immune therapy” that enhance immune responses and amplify the healing power of individual patients. After analysis of human genomic, much attention is paid to the individual properties due to the individual genomic information and it is becoming more popular to treat the individual cancer patients using personalized anti-cancer drugs due to their genomic information, called as a personalized l therapy. On the other hand, immune system plays an inevitable role for defending our body from the infectious diseases or cancers. Recently, much attention is focused on the application of immune function to treat infectious diseases, cancers, as well as other diseases.
One example is to development antibody therapeutic drugs to treat infectious diseases and autoimmune diseases. Another example is development of cellular therapy using T lymphocytes to treat cancer patients. In these strategies, personalized therapy is an important issue.
For example, since viruses such as HIV or influenza rapidly changes their antigenecities (epitopes) to escape from immune system, individual immune therapy for individual patients becomes inevitable. Cancers in individuals also exhibit their individual characteristics, so that personalized therapy is necessary for cancer patients. Furthermore, individual MHC (major histocompatibility complex), whose properties are totally different in each individual i.e. personalized), is essential for antigen recognition by T lymphocytes. Thus, it is conceivable that immune therapy is personalized therapy (in other word, tailored therapy), itself.
Immune therapy for the personalized medical treatment foe infectious diseases and caners consists of two methods: one is antibody therapy and the other T cell therapy. In antibody therapy, we amplify antibodies against viruses or cancer cells . In T cell therapy, we amplify T lymphocytes attacking cancer cells in patients. Both methods enhance immune system of individual patients.
In this project, we try to unfold the rapid antibody generating system that we have previously developed and simultaneously develop a novel system in which we detect antigen-specific T lymphocyte for infectious microbes or cancer cells in blood or tissues of patients, isolate TCR genes, assay their functions, and generate recombinant TCR protein or express the functional TCR on lymphocytes to use them for diagnosis and therapy for patients suffering from infectious diseases or cancer. We combine the antibody therapy and T lymphocyte therapy to develop the personalized immune medical treatment.
Using micro-well array chip, we can screen comprehensively live lymphocytes and detect very rare antigen-specific lymphocytes in peripheral blood or tissues. We establish fundamental techniques to generate antigen-specific B lymphocytes as well as T lymphocytes and obtain the patents. By transferring the patents to SCW (Single Cell World) Co., a venture established in Toyama, we promote the company to commercialize them.
We analyze functions of the newly developed-antibodies, TCRs or fsTCRs (functional soluble TCRs) and obtains patents, licenses to corresponding enterprises. We try to establish a research base for personalized medical treatment for infectious diseases and cancers and launce a lodgment for antibody- and T lymphocyte-mediated immune therapy in Hokuriku area.
Furthermore, by generating enormous numbers of human antibodies, that certainly contain many candidates or seeds for the antibody therapy, we may contribute antibody-based medical therapy in the world.