Where is the next leap in CAR-T therapy? Cinda Bio and other Chinese companies explore new directions

The arrival of CAR-T therapy is a milestone in the field of cancer treatment.

Public information shows that in order to benefit more cancer patients, including solid tumors, scientists are developing some new CAR-T therapies.

1.

CAR-T therapy targeting BCMA targets multiple myeloma cells by engineering the patient's T cells in vitro to express CARs specific to BCMA.

Reindeer Medical/Cinda Bio: CT103A (IBI326)

CT103A is a fully human BCMA chimeric antigen receptor autologous T cell injection jointly developed by Reindeer Medical and Innovent.

CT103A uses lentivirus as a gene vector to transfect autologous T cells.

Legendary creatures/Janssen: LCAR-B38M (JNJ-4528)

LCAR-B38M is a CAR-T therapy targeting BCMA jointly developed by Legend Biotech and Johnson & Johnson's Johnson & Johnson company.

In China, LCAR-B38M has been included in the breakthrough therapy category by NMPA.

Keji Bio: CT053

CT053 is a CAR-T cell therapy targeting BCMA independently developed by Keji Biotech.

2.

The CT041 independently developed by Keji Biologics is a humanized anti-CLDN18.

Three, dual-targeted CAR-T therapy

Although a single antigen CAR-T cell has shown significant clinical efficacy, it is still observed in clinical trials that a large number of patients have problems such as antigen escape and high recurrence rate.

CD19×CD22 dual target CAR-T therapy

CD22 is one of the inhibitory co-receptors on the surface of B cells, and it is expressed on the surface of most B cell malignant tumor cells.

Hengrun Dasheng’s anti-human CD19-CD22 T cell injection is a genetically engineered autologous CAR-T cell product targeting CD19-CD22 targets.

GC022F from Genxi Biosciences is also a CAR-T therapy targeting CD19 and CD22 developed based on Genxi Biotech’s FasTCAR platform.
Studies have shown that compared with traditional dual CAR-T cells, FasTCAR™ technology can successfully produce anti-CD19/CD22 dual-targeting CAR-T cells within 24 hours, with younger phenotypes and fewer T cell failures.
The xenograft mouse model also showed better efficacy.

BCMA×CD19 dual-targeting CAR-T therapy

Genxi Biologics GC012F is a CAR-T therapy that targets both BCMA and CD19.
At the 2020 ASH conference, Genxi Biotech reported the early results of a first human trial (FIH) multi-center clinical study of GC012F in patients with relapsed/refractory multiple myeloma.
The data showed that 15 of the 16 patients at all dose levels responded to the treatment, with an ORR of 93.
8%, and the earliest response was observed on the 28th day; at the same time, the data showed that the candidate drug also has good safety.

4.
Off-the-shelf allogeneic CAR-T therapy

As we all know, most CAR-T therapies need to obtain T lymphocytes from patients for genetic engineering and then inject them back into patients.
This production process is not only complicated, but also time-consuming and labor-intensive, which affects the CAR-T therapy to a certain extent.
widely used.
"Ready-to-use" allogeneic CAR-T therapy is to obtain T cells from healthy donors for genetic engineering.
The generated CAR-T cells can be frozen and stored, and can be directly injected into patients when needed.
.
Therefore, it is possible to solve the above-mentioned problems currently faced by CAR-T therapy.

At present, many Chinese companies are developing allogeneic CAR-T therapies, including Keji Biology, Hengrun Dasheng, Genxi Biology, Reindeer Medical, Boya Gene, Linglu Pharmaceutical and so on.
Among them, Linglu Pharmaceutical is a cutting-edge company that just announced its official sailing in December 2020.
The joint venture established by the company and Allogene Therapeutics will develop a number of products targeting BCMA, CD70, FLT3 and Singapore in Greater China, South Korea and Singapore.
DLL3's ready-to-use allogeneic CAR-T (AlloCAR-T™) therapy is used for the treatment of blood cancers and solid tumors, and promotes the global development of these AlloCAR-T therapies.

Five, a new era of various CAR cells

It is worth mentioning that studies have found that CARs targeting tumor antigens can not only be expressed on T cells, but also on NK cells and macrophages, making these cells a weapon to attack solid tumors.
These new therapies are called CAR-NK, CAR-M.
A study published in the New England Journal of Medicine (NEJM) in 2020 showed that 11 cancer patients received a CAR-NK therapy targeting CD19, and none of them had the common toxic effects of CAR-T therapy.

In China, some companies have begun to pay attention to the new type of CAR-NK therapy, including Hengrun Dasheng, Guojian Chengnuo Biological, and Boshengji Pharmaceutical Technology.
Among them, the clinical trial application of "Targeting Mesothelin Chimeric Antigen Receptor NK Cell Injection" of Guojian Chengnuo Biologics has been accepted by CDE in February 2020.
According to the press release, this is the first CAR-NK therapy for solid tumor treatment to be declared clinically in China.

The potential advantages of CAR-M therapy have also been initially verified in preclinical studies.
In 2020, a study published by scientists at the University of Pennsylvania showed that CAR-M therapy successfully reduced tumors in animals and prolonged their lifespan in a mouse model of HER2-positive metastatic ovarian cancer.
On March 18, 2021, a CAR-M therapy developed by CARISMA Therapeutics has completed the first patient administration.
It is reported that this is the first CAR-M therapy to enter the clinical stage.

The authoritative academic journal "Nature-Medical" has listed CAR-NK therapy and CAR-M therapy as one of the ten notable developments in the biomedical field in 2020.
"Nature-Medical" commented that these advances mean that "cancer treatment ushered in a new era of CAR cells.
"

Reference

[1] The clinical data of BCMA CAR-T jointly developed by Innovent Bio and Reindeer Medical was unveiled at the ASH Annual Meeting.
Retrieved Dec 10, 2019, from http://innoventbio.
com/#/news/183

[2] The first in China! Hengrun Dasheng dual-target CAR-T registration was successfully clinically approved, opening a new journey of tumor immunotherapy.
Retrieved Jan 08, 2021, from http:// style="vertical-align: inherit;">[3] The clinical application of Guojian Cheng Nuoyi's spot-type CAR-NK cell product from peripheral blood was accepted by the State Food and Drug Administration.
Retrieved Feb 9, 2021, from https://mp.
weixin.
qq.
com/s/xM2Pmr5eZCNM6wacgwRCfQ

[4] Official public information of each company