All-round view of the CD30 target: ADC is a hit, but the red double antibody has no fruitful CAR...

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CD30 is a member of the tumor necrosis factor (TNF) receptor superfamily, which can promote cell proliferation or apoptosis by activating different signaling pathways.

In 2020, Verbutuximab for injection (Adcetris) was approved for marketing in China, and CD30 became famous.

01, CD30

Research and development found that CD30 is closely related to cell proliferation and death.

In healthy cells, CD30 is not expressed, but is low on the surface of normally activated T cells and B cells.

Although CD30 has the characteristics of low expression in healthy cells and high expression in tumor cells, the performance of anti-CD30 drugs that enter clinical trials is not very satisfactory.

02, CD30 ADC

The trade name of Brentuximab Vedotin is Adcetris.

Adcetris is an antibody-conjugated drug (ADC) targeting CD30, which consists of three components: (1) Human-mouse chimeric monoclonal antibody Brentuximab targeting CD30; (2) Citrulline-valine random couple Linked dipeptide linker; (3) Small molecule drug MMAE (Auristatin E), DAR=4.

When Adcetris binds to the tumor cell membrane CD30 receptor, Adcetris is internalized into the lysosome mainly through clathrin-mediated endocytosis, and then the dipeptide is hydrolyzed and broken by protease, and finally MMAE binds to the cytoplasmic tubulin to block it.

Data source: Seattle Genetics

Adcetris was approved by the FDA in 2011 and approved by the NMPA in 2020.

Data source: Seattle Genetics

The only domestic deployment of CD30 ADC is the F0002-ADC of Fudan Zhangjiang/cross-linked drug.

Data source: CDE

03, CD30 double antibody

There is currently no drug approved for CD30 double antibody, and Affimed's AFM13 is the top clinical one.

AFM13 is a tetravalent tandem CD16A×CD30 double antibody with a molecular weight of 100KD.

AFM13 can mediate the specific and selective killing of CD30-positive cells by macrophages and NK cells, that is, kill tumors through ADCC and ADCP.

The study also found that after binding to NK cells, AFM13 remains on the surface of NK cells, making it anti-CD30-positive cells-Karpas299 CAR characteristics.

Data source: Affimed

04, CD30 CART

CART cell therapy is currently one of the hottest research directions in the field of tumor cell immunotherapy.

At present, the domestic companies that have deployed CD30 CART cell therapy research include Eucardi, Porida and Imming Cell.

In May 2019, Shanghai Ucardi Biomedical Technology Co.
, Ltd.
CD30 CAR-T obtained a patent authorization from the State Intellectual Property Office, becoming the first company in China to obtain a CD30 CAR-T invention patent.
In April 2020, Boruida Bio-targeted CD30 chimeric antigen receptor gene-modified autologous T cell injection (BRD-01) was approved clinically for the treatment of CD30+ relapsed/refractory hematological tumors aged 18 to 70 , Is the first clinically approved CAR-T cell therapy targeting CD30 in China.
Imming Cell has taken the lead in the world to carry out clinical research on CD30 CAR-T cell therapy for the treatment or adjuvant treatment of Hodgkin’s lymphoma and anaplastic large cell lymphoma or other CD30-positive tumors.
The non-registered clinical trials that have been carried out have proved that, Its effective response rate is 92%, and the overall CR rate has reached the industry-leading level.