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Progress in CAR-T therapy for domestic corporate entities in 2022

 Last Update: 2022-10-01
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Over the years, whether it is a 100% initial response rate or a significant increase in 5-year survival rate, CAR-T cell therapy has achieved remarkable results
in the treatment of blood cancer.

However, the breakthrough of CAR-T in the field of solid tumors is very challenging, the main reasons are the difficulty of selecting targets, the difficulty of CAR-T cells entering the tumor solid, and the fact that they are blocked by other immune molecular living cells after entering the tissue
.

Today we will take stock of the progress
made by domestic enterprises in the field of CAR-T therapy for the treatment of solid tumors in 2022.

In 2022, domestic enterprises have made progress in the field of CAR-T therapy in the treatment of solid tumors

1 Keji Pharmaceutical——CT041, CT053

Keji Pharmaceutical is undoubtedly the enterprise with the largest layout and the most rapid progress of CAR-T therapy pipelines in China
.

CT041 and CT053, the enterprises with the largest layout and the most rapid progress of solid tumor CAR-T therapy pipelines in China

CT041

CT041 is a potential "first-in-class", CLDN18.

CLDN18.

In May, the results of the Phase I midterm analysis of the CT041 investigator-initiated trial were published in the international journal Nature Medicine
.

The results of the midterm analysis of the I issue were published in the international journal Nature Medicine 48.

Screenshot source: Nature Medicine

At the beginning of this year, CT041 has been approved by the State Food and Drug Administration of China to enter the confirmatory phase II clinical trial, which is the world's first and only CAR-T product that has entered the confirmatory phase II clinical trial and is under research for solid tumors
.

This is the world's first and only confirmed Phase II clinical trial, and the CAR-T product under research for solid tumors is also scheduled to launch a key Phase II clinical trial in the United States this year

CT053

CT053 is an upgraded whole-human anti-BCMA autologous CAR-T cell candidate for the treatment of relapsed/refractory multiple myeloma
.

On July 19 this year, Kelun Pharmaceutical announced that the results of a CT053 trial for the treatment of relapsed/refractory multiple myeloma (R/R MM) have been published
in the journal Haematologica.

CT053 is well tolerated overall, without the occurrence of ≥ grade 3 cytokine release syndrome (CRS).

Image source: https://haematologica.

In addition, CT053 has now completed the enrollment of key phase II clinical trials in China; and has begun critical Phase II clinical trials
in North America.

Completed the enrollment of key Phase II clinical trials in China; It has begun conducting key Phase II clinical trials in North America this year to the State Food and Drug Administration of China and the US FDA in 2023 to submit regulatory applications for marketing approval

2 Proto-Enlightenment - Ori-CAR-001, OriCAR-017

Ori-CAR-001

Ori-CAR-001 is a new generation of GPC3-targeting autologous chimeric antigen receptor T cells with the primary indication for the treatment of relapsed/refractory hepatocellular carcinoma (HCC
).

In humans, the GPC3 protein expressed by the GPC3 gene has significant differences in expression in different developmental periods and different tissues, such as low expression or non-expression in gastric cancer, breast cancer, ovarian cancer and other cancers, and is often overexpressed
in hepatocellular carcinoma.

Many studies believe that GPC3 has great potential in liver cancer immunotherapy

In July this year, the official website of the Drug Review Center (CDE) of the State Food and Drug Administration showed that the clinical application of Ori-CAR-001 (acceptance number: CXSL2200304) was accepted
.

The clinical application for Ori-CAR-001 (acceptance number: CXSL2200304) was accepted

Screenshot source: CDE official website

OriCAR-017

In June this year, at the 2022 ASCO Annual Meeting, Yuanqi Bio published the Phase I POLARIS clinical trial data conducted by researchers of OriCAR-017 (autologous GPRC5D-targeted chimeric antigen receptor T cells) for the treatment of relapsed refractory multiple myeloma (RRMM) in the form of an oral presentation[4].

The results showed that OriCAR-017 showed good safety and efficacy
in patients with RRMM.
Most AEs are transient and manageable, with 100% ORR, 100% MRD negative rates, and favorable safety supporting OriCAR-017 as a potential regimen for
the treatment of RRMM.
At the same time, this is also the first time in China to publish clinical data
on CAR-T therapy for GPRC5D targets.

For the first time in China, clinical data on CAR-T therapy for GPRC5D targets were published

At present, Yuanqi Bio is accelerating the registration and clinical development of the drug in China and the United
States.

3 Shanghai Stanser Bio - GCC19CART

GCC19CART

GCC19CART is a CAR-T cell therapy based on Stansé's self-developed CoupledCAR® technology platform for solid tumors that targets antigen guanylate cyclase 2C (guanylate cyclase 2C, GCC or GUCY2C) to treat patients with
relapsed/refractory colorectal cancer (R/R mCRC).

About 80% of colorectal cancer patients have positive
GCC expression in their tumors.
In recent years, studies have found that GCC is stably expressed in primary coloral cancer cells and abnormally high in metastatic coloral cancer cells, which is considered to be one of
the specific marker molecules for metastatic colorectal cancer.

About 80% of colorectal cancer patients have positive GCC expression in their tumors that are considered one of the specific marker molecules for metastatic coloral cancer

In May, at the 25th Annual Meeting of the American Society for Gene and Cell Therapy (ASGCT), Stanser unveiled multicenter clinical data for the treatment of relapsed/refractory colorectal cancer (R/R mCRC), a candidate product developed based on its self-developed CoupledCAL® platform technology
.
GCC19CART has shown good clinical initial efficacy and acceptable safety
in patients with R/R colorectal cancer.

Demonstrated good clinical initial efficacy in relation to the dose as well as acceptable safety

In addition, Stanser plans to launch Phase I clinical trials in the United States in the middle of this year, mainly to evaluate the safety, tolerability and efficacy of GCC19CART in patients with relapsed refractory metastatic colorectal cancer
.

In the middle of this year, Phase I clinical trials will be launched in the United States

Summary

There are currently about 40 targets of solid tumor CAR-T in clinical trials, of which Claudin 18.
2, MSLN, GPC3, HER2, PSMA, EGFRvIII, EpCAM, CEA, and Mesothelin account for more than
60% of the total clinical number.

More than 60%.

From the current clinical data, classical targets such as HER2 and GD2 have not observed a good clinical response, and targets such as Claudin18 and GPC3 show a certain clinical response
.
Moreover, the histopathological characteristics of solid tumors, the lack of tumor-specific antigens, the immunosuppressive tumor microenvironment (TME), potentially life-threatening targeting, and exotoxicity of tumors and other unique challenges make CAR-T progress on solid tumors very slow
.

Histopathologic features of solid tumors, lack of tumor-specific antigens, immunosuppressive tumor microenvironment (TME), potentially life-threatening targeting, and exotoxicity of tumors

Still, scientists are trying to overcome some of these hurdles to better overcome the conundrum
of solid tumors.
We look forward to the solid tumor one day, which will be broken by scientists! In the current field of solid tumors, CAR-T cell therapy is almost always in phase I trials to verify whether it is safe; However, there are also NK, CIK, DC-CIK and other cellular immunotherapies that have matured and are widely used in clinical practice
.
(Source: Sheng Jie Frontiers, Cell and Gene Therapy)

Resources:

[1]http://t.
10jqka.
com.
cn/pid_189462165.
shtml

[2]http://sh.
xinhuanet.
com/2022-05/10/c_1310588992.
htm

[3]https://zhuanlan.
zhihu.
com/p/543319271

[4]https://m.
21jingji.
com/timestream/html/%7BAaxZlHfBm9s=%7D

[5]

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