Tumor immune cell therapy in Yi Hao

The research and development of Yihao's biological tumor immune cell therapy is at the forefront in China. We have developed platforms for the amplification and

transduction of CAR-T, TCR-T and CAR-NK. Currently, the company has established a complete CAR-T production process such as plasmid construction, preparation and

transduction of viral vectors, separation of peripheral blood cells, cell activation, and cell expansion. At the same time, it can accurately control the key process points in the

production process.

CAR-NK Cell

CAR-T cell therapy

CAR-T Technology：

As a burgeoning therapy for neoplasm, the development of CAR-T cells therapy has made non-negligible progress, making immune therapies for tumors enter on a new

stage. 
Chimeric antigen receptor (CAR) is a modular fusion protein comprising extracellular target binding domain usually derived from the single-chain variable fragment (scFv) of

antibody, spacer domain, transmembrane domain, and intracellular signaling domain containing CD3z linked with zero or one or two costimulatory molecules such as CD28,

CD137, and CD134. T cells engineered to express CAR by gene transfer technology are capable of specifically recognizing their target antigen through the scFv binding

domain, resulting in T cell activation in a major histocompatibility complex (MHC)-independent manner.

General procedure for CAR-T treatment：

Cells of interest are isolated from the whole blood of a patient, followed by enrichment, activation and expansion. At the time

of activation, the lentiviral vector is added. On the final day of culture, cells are harvested and cryopreserved in an infusible

media. The patient is infused with gene-modified cells and endpoint assays are conducted at designated time intervals. At the

conclusion of active monitoring, the patient is transferred to a destination protocol for long-term follow-up as per FDA guidelines.

CAR-NK Cell Therapy

Natural killer (NK) cell-mediated cytotoxicity contributes to the innate immune response against various malignancies. The antitumor effect of NK cells is a subject of intense

investigation in the field of cancer immunotherapy.
CAR-NK cells hold great promise as a novel cellular immunotherapy against refractory malignancies. Notably, NK cells can provide an “off-the-shelf” product, eliminating the

need for a personalized and patient-specific product that plagues current CAR-T cell therapies. The ability to more potently direct NK cell-mediated cytotoxicity against

refractory tumors through the expression of CAR is likely to contribute to the recent paradigm shift in cancer treatment.

Advantages of CAR-NK Cell Therapy：

There are several advantages to using CAR-NK cells compared to T cells. For example:
Adoptively transferred autologous and allogeneic NK cells have limited in vivo persistence. 
The lack of clonal expansion of NK cells and immune-mediated rejection of allogeneic NK cells within days to weeks makes life-threatening toxicities such as cytokine release syndrome

(CRS) less likely. 
Furthermore. NK cells do not cause GVHD, Thus, NK cells offer opportunities to produce an off-the-shelf allogeneic product that could be readily available for immediate clinical use.
Additionally, unlike CAR-T cells, CAR-NK cells will retain their intrinsic capacity to recognize and target tumor cells through their native receptors, making disease escape through

downregulation of the CAR target antigen less likely than it is with CAR-T cells.

TCR－T Cell Therapy

TCR－T

T-cell receptors (TCRs) can be genetically modified to improve gene-engineered T-cell responses, a strategy considered critical for the success of clinical TCR gene therapy to treat cancers. 
TCRs consist of an α and β chain non-covalently associated with the CD3 complex on the T cell surface. Activation of T cells occurs when the TCR recognizes peptides non-covalently bound to major histocompatibility complex (MHC) on the surface of

antigen-presenting cells or tumor cells.

General procedure for TCR-T treatment