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Technology: 1

CAR-T cell therapy

Autologous CAR-T cell therapy


Hybrid CAR

New Adoptive T Cell Transfer Approach

Chimeric Antigen Receptor (CAR)  T cells use antibodies to recognize antigen proteins on the cancer and oftenly normal cell surface.  Inside T cell there is a molecule called intracellular signaling domain,  enhancing its activity. 

Approved CAR-T cells` breakthrough efficacy against hematological B cell tumors is accompanied with high on-target/ off-tumor toxicity because target antigens are expressed on both cancer and normal B cells. Basically, current CAR-T cells indiscriminately attack cancer and normal B cells marked by targeted antigen. 

TCR-T cell receptors recognize cancer-specific antigen derived peptides expressed in complex with HLA on cancer cell surface and attack them.  Initially naive cancer-specific receptors were transferred to T cells with some modest results. Nowadays cancer-specific receptors with enhanced affinity are mostly used in TCR-T cells clinical studies.  So TCR-T cell approach is more cancer-specific, but yet to demonstrate comparable results for solid tumors.    

Our exceedingly powerful and precise Hybrid CAR-T cell therapy combines CAR-T cell power with TCR-T cell precision.


Adapted from Cell Immunotherapy (Layout), by (2022). Retrieved from

Problem and solution

Currently several effective CAR-T cells have been approved for hematological tumors. However, none of CAR-T cells have proven to be sufficiently effective against solid tumors, including ones in the development stage. It is because of the low receptor specificity and declining activity of T cells in immunosuppressive tumor microenvironment.

Affinity enhanced TCR approach is widely used against solid tumors, though it is limited only to modification of the receptor outside the cell without modifying the inner cell.

So we designed next generation Hybrid CAR-T cell with uniquely cancer-specific CAR and novel intracellular signaling domain for strong and persistent anti-tumor activityOur approach demonstrates promising results in preclinical studies and is being clinically tested now.


Adapted from Cell Immunotherapy (Layout), by (2022). Retrieved from

Technology: 2

Hybrid CAR-T Cell Features

Original Hybrid CAR Targeting Intracellular Antigen Peptides

We apply TCR like gene transfer technology to enhance the recognition of intracellular cancer-specific antigen molecules expressed on the cancer cell surface in HLA/MHC areas.

Our partner laboratory in Mie University discovered an antibody and designed a CAR with enhanced antigen specificity of the scFv (anti-pMHC) part to recognize the complex (pMHC) of HLA-A*0201 and MAGA-A4 antigen derived peptide, frequently expressed on solid cancer cells. 

Similarly, for the PRAME antigen, we increased the HLA-A*2402 complex (pMHC) antigen specificity. As a result, it exhibits a high specificity for solid cancer intracellular antigen, and is expected to increase the therapeutic effect.


Adapted from Cell Immunotherapy (Layout), by (2022). Retrieved from

Discovery of GITR co-stimulation signal molecule improving cell activity

The first-generation CAR structure consists of a single-chain antibody (scFv) that recognizes the surface antigens of tumor cells, a transmembrane domain, and an intracellular domain of the TCR complex that activates T cells.

In the second generation, the intracellular domain of the T cell co-stimulator molecule was added to enhance T cell activation.

The third generation linked the intracellular domain derived from the tumor necrosis factor receptor. 

Consequently CARs targeting various tumor antigens have been researched and developed. However, the co-stimulation signal molecules used as the intracellular domain in CAR are limited, and rare ones have cytotoxic activity and effective co-stimulation signal.

T Cell Nouveau  CAR-T has the intracellular domain of glucocorticoid-induced tumor necrosis factor receptor (GITR), which is one of the costimulatory signal molecules with high cytotoxic activity against targeted cancer cells.

T cells proliferation rate increased by including GITR intracellular domain. In addition, inhibition of regulatory T cells immunosupressive function helps maintain persistent in vivo anti-tumor activity, resistance to the tumor microenvironment immunosuppression, resulting in excellent tumor growth-suppressing action. 

Technology: 3
Technology: 3.1
Technology: 4

Automatic Cell Processing

Automatic cell manufacturing and benefits

T Cell Nouveau commits to delivering Hybrid CAR-T cells to medical institutions faster at reduced manufacturing costs. To achieve this, we are developing an automatic cell processing All-In-One Cell Processing Unit (CPU).


Standard equipment is used for the automatic cell processing, enabling a simple design at smaller space with fewer manpower operation, eventually, shortening the manufacturing time and reducing costs.

Benefits of automation

  • Quick delivery time

  • High reproducibility and low cost

  • Easy technology transfer and scale up

Novel CAR-T cells with novel signaling domain
GITRL secreting co-stimulatory signal molecules
to enhance therapeutic effects 

In order to further enhance the effects of the GITR intracellular domain, we created a new GITR Ligand-releasing CAR-T. Along with the release of GITRL due to stimulation of CAR, it not only promotes its own activation via GITR receptor (autocrine), but also activates surrounding immune cells due to paracrine effects.

This time, we applied this new domain to the design of GD2 CAR-T, which uses our proprietary GD2 antibody as the receptor. GD2 is a glycolipid mainly expressed on the surface of nerve cells, and overexpression has been confirmed in neuroblastoma, a type of childhood cancer, triple-negative breast cancer, melanoma, etc. Additionally, our antibody portion specifically recognizes GD2 and has been confirmed to have low reactivity to related glycosphingolipids.


Adapted from Cell Immunotherapy (Layout), by (2022). Retrieved from


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Mitsui J, Nishikawa H, Muraoka D, Wang L, Noguchi T, Sato E, Kondo S, Allison JP, Sakaguchi S, Old LJ, Kato T, Shiku H. Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals. Clin Cancer Res. 2010 May 15;16(10):2781-91. doi: 10.1158/1078-0432.CCR-09-3243. Epub 2010 May 11. PMID: 20460483.


Imai N, Ikeda H, Tawara I, Wang L, Wang L, Nishikawa H, Kato T, Shiku H. Glucocorticoid-induced tumor necrosis factor receptor stimulation enhances the multifunctionality of adoptively transferred tumor antigen-specific CD8+ T cells with tumor regression. Cancer Sci. 2009 Jul;100(7):1317-25. Doi: 10.1111/j.1349-7006.2009.01179.x. Epub 2009 Apr 29. PMID: 19432889.


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