The TCR-T therapy that makes up for the shortcomings of CAR-T is favored by capital and has a promising prospect

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# News Review #

# News Review #

On August 3, T-knife Therapeutics announced that it has completed a Series B financing of US$110 million
.

The funds obtained will be used to advance its T cell receptor (TCR)-T cell therapy into clinical development, expand its scientific research team and improve manufacturing capabilities

TCR (T cell receptor), a specific receptor on the surface of T cells, binds to CD3 with non-covalent bonds to form a TCR-CD3 complex, which activates T cells by recognizing and binding antigens presented by MHC, and promotes T cell growth.
Division and differentiation
.

The mechanism of TCR-T is to introduce new genes into ordinary T cells, so that the modified T cells can express TCR that effectively recognizes tumor cells, thereby guiding T cells to kill tumor cells
.

The basic treatment process is to isolate immunocompetent cells from tumor patients, perform amplification and functional identification in vitro, and then return them to the patient, so as to achieve the goal of directly killing the tumor or stimulating the body's immune response to kill the tumor cells

TCR-T treatment process (Source: Xiangxue Pharmaceutical official website)

T-knife Therapeutics’ TK-8001 is developed using the company’s humanized T cell receptor (HuTCR) mouse platform.
The mice produced by this platform carry the gene sequence expressing human TCRαβ and express a variety of human leukocyte antigens ( HLAs)
.

Mice vaccinated with human tumor autoantigens will treat these antigens as foreign tissues, resulting in targeted, high-affinity optimized TCRs

Diagram of HuTCR transgenic mouse technology platform (Source: T-knife official website)

Specializing in solid tumors

Specializing in solid tumors

TCR-T makes up for the shortcomings of CAR-T

TCR-T makes up for the shortcomings of CAR-T

Since CAR-T (Chimeric Antigen Receptor T Cell) therapy was launched in 2017, cell therapy has officially entered the medical and health arena.
The industry is experiencing rapid growth and investment worldwide
.

Although CAR-T cell therapy has shown extraordinary efficacy in blood diseases, the development of solid tumors faces challenges

Both TCR-T and CAR-T are adoptive immune cell therapy, that is, immune cells are separated from tumor patients, genetically modified and amplified in vitro, and then injected back into the patient
.

But their mechanisms for recognizing antigens are completely different

CAR-T cells use antibody fragments that bind to specific antigens on the surface of cancer cells
.

TCR-T cells can recognize tumor-specific antigens derived from the cell membrane surface or intracellularly, and can target most tumor-specific antigens, especially those tumor cell antigens

Becoming a research hotspot

Becoming a research hotspot

Many domestic pharmaceutical companies deploy TCR-T therapy

Many domestic pharmaceutical companies deploy TCR-T therapy

The global TCR-T therapy is mainly aimed at the solid tumor market and has become a research hotspot in the world
.

According to incomplete statistics, there are currently 53 drugs at the clinical or higher stage at home and abroad.

⚪Xiangxue precision

Xiangxue Precision Medical Technology Co.
, Ltd.
(referred to as Xiangxue Precision) was established in 2015.
It is a pharmaceutical company with internationally leading cutting-edge biotechnology as a starting point for cellular immunotherapy
.

Mainly dedicated to the research and development of TCR-T immunotherapy technology with China's independent intellectual property rights

At present, a full coverage R&D platform has been established from TCR-T product R&D, preparation, quality control, product industrialization to clinical transformation, and a product pipeline covering most of the population's genotypes
.
The first product, TAEST16001 injection, has been approved by the State Food and Drug Administration to enter the clinical trial of a new drug.
It is the first TCR-T cell drug in China to enter the clinical trial of the registration system
.

⚪Tenkoya

Guangdong Tiankeya Biomedical Technology Co.
, Ltd.
(Tiankeya for short) focuses on the research and development and industrialization of tumor immune cell therapy.
Its TCR/CAR-T development platform, virus and cell transformation and production technology platform are in an international leading position
.
The company has established three core platforms:

TRUST platform: Original TCR screening platform to solve the pain points of lack of targets
.
The artificial intelligence high-throughput single-cell screening platform can clone and target TCR within 6 weeks, far exceeding the industry average
.

CHECK-T cell transformation platform: CHECK-T cell transformation platform helps the pain points of immune suppression
.
A new generation of T cell drugs loaded with immune checkpoint inhibitory molecules is expected to significantly improve the therapeutic effect of solid tumors
.

TURBO-T cell transformation platform: the ultimate weapon to challenge the heterogeneity of tumor cells
.
Innovative T cell drugs are loaded with tumor microenvironmental transformation factors to stimulate broad-spectrum anti-tumor immunity to combat heterogeneity
.

The company's first batch of pipelines to enter clinical trials are for tumors caused by viral infections, such as EBV and HPV, which are currently in phase II
.

⚪Kerui Bio

Kerui Biotech was established in 2015.
Its core product is Universal TCR-T (UTCR-T).
Currently, it has completed the establishment of key technology platforms and early products, and has begun planning and applying for core patents
.

Kerui Bio has established a relatively complete TCR-T research and development technology system, covering specific tumor antigen screening and identification, T cell immune epitope identification, epitope-specific TCR cloning, TCR affinity optimization and TCR preclinical verification and other technology platforms.
A clinical trial of TCR-T for the treatment of lung cancer has been initiated
.

TCR-T therapy

TCR-T therapy

Huge market potential

Huge market potential

Affected by changes in various factors such as economy, society, environment and life>
.
The China Investment Consulting Industry Research Center predicts that 10% of new cancer patients will choose CAR-T and TCR-T immune cell therapy.
According to the price of 300,000 per person, CAR-T and TCR will be used by 2023.
-T tumor cell immunotherapy market scale can reach 160 billion yuan
.

TCR-T therapy is currently still in the experimental stage, and further research and improvement are needed in the future, including how to effectively target and screen TCR, and how to conduct a reasonable TCR-T clinical trial design
.
At present, there are no related products on the market at home and abroad
.
If the research and development goes well, it is expected to be approved for listing by the end of 2022
.
I hope that in the near future, through the unremitting efforts of scientific researchers and enterprises, TCR-T therapy will surely play an important role in solid tumors and other fields
.

refer to:

1.
T-knife Therapeutics Announces $110 Million Series B Financing to Advance Pipeline of T-cell Receptor Therapies.
Retrieved August 2, 2021, from https:// /0/en/T-knife-Therapeutics-Announces-110-Million-Series-B-Financing-to-Advance-Pipeline-of-T-cell-Receptor-Therapies.
html.

2.
Liu Q et al.
Cancer immunotherapy using T-cell receptor engineered T cell.
Annals of Blood (2020).

3.
http://