Johnson and Johnson, Sanofi, etc. are developing CD38 antibody development prospects and anti-cancer potential?

Recently, China CD38 antibody research field ushered in a lot of progress.
July, Johnson and Johnson's CD38 monoail submitted two applications for listing in China for new adaptive disorders; Sanofi's CD38 synth was granted two clinically implied licenses in China; and the CD38 monoathropoly clinical application of Chinese company Shang Jian Bio was accepted in late July.
CD38 has become one of the current hot targets.
two CD38 monotherapy units have been approved worldwide for the treatment of multiple myeloma (MM).
In China, only Johnson and Johnson's Daleimu monoantigen this CD38 monoantigen has been approved, but also a number of targeted CD38 antibodies into clinical trials or declaration of clinical stage, these products in research mainly from Sanofi, Tiandi Biological, Shangjian Bio, Youzhiyou Bio and other companies.
, why is CD38 a target for the development of antibody drugs for multiple myeloma, and what is its potential for development and treatment? Cd38's biological effect CD38 antigen was discovered in 1980 and is a type II trans-membrane glycol protein of 46 kDa size.
CD38 is CD31, also known as PECAM-1, which is a member of the Ig gene super-family.
CD31 is expressed in lymphocytes (follicle membrane B cells and plasma cells), the lungs (alps, alps and lymphatic tubes) and the kidneys (renal ball cells) in addition to endometrial cells.
cd38 interacts with the dosser CD31 and plays an important role in regulating cell migration, receptor-mediated adhesion, and signal conduction.
addition, CD38 protein is a dual-functional extracellulase that combines the activity of cycloenzyme and hydrolytic enzymes and participates in nucleotide metabolism.
CD38 uses NAD plus as a substrate to form ring ADP rnabolites (cADPR) and ADPR, which are effective second messengers that regulate the mobilization of Ca ions in the cytoste and activate signaling paths that control various biological processes, such as lymphocytic proliferation, pancreatic B cell secretion insulin, and so on.
also studies have shown that the production of CD38-dependent adenosine plays a key role in immunosuppression mediated by natural killer (NK) cells.
, CD38 is expressed at low levels in normal lymphocytes and myelin cells, as well as in non-hematopoietic tissue, and is widely expressed in cells of hematopoietic origin, including stereotyped stem cells.
because CD38 is expressed in B cells, cd38 expression levels in plasma cells (also known as effect B cells) are particularly high.
expression of CD38 is associated with a variety of diseases, including AIDS, autoimmune diseases such as systemic lupus, type 2 diabetes, osteoporosis and cancer.
study found that CD38 is highly expressed in a large number of malignant blood cancers, especially in cancers such as multiple myeloma, which makes CD38 a target for the development of therapeutic antibody drugs for multiple myeloma.
two CD38 synths have been approved worldwide, and research on Synoptic and Sanofi-targeted CD38s began in 1990.
Worldwide, two CD38 monotherapy units have been approved for sale, Daratumumab, developed by Janssen Pharmaceuticals of Johnson and Johnson, and Isatuximab of Sanofi, which are coming to offer new treatment options for patients with multiple myeloma.
studies have found that CD38 antibodies kill tumor cells primarily through the Fc-dependent immune effect mechanism, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell phagocytosis (ADCP), and apoptosis.
addition, CD38 antibodies can improve host anti-tumor immunity by eliminating regulatory T-cells, regulatory B-cells, and myelin-like-sourced inhibitory cells. the mechanism of action of
CD38 monotherapy multiple myeloma (Photo source: Resources: 2) Jansen Pharmaceuticals' Daremu monotherapy was first approved by the FDA in November 2015 to treat patients with multiple myeloma, the world's first approved all-human monoclonal antibody targeting CD38.
According to an earlier press release issued by Jansen Pharmaceuticals, Daremu monoantiability specifically identifies CD38, which is highly expressed on multiple myeloma malignant plasma cells, and thus induces the death of tumor cells through a variety of immuno mediated mechanisms.
since its inception in 2015, Darrem monotherapy has been approved by the FDA several times to expand the scope of treatment for patients with multiple myeloma.
Sanofi's isatuximab is a monoclonal antibody that targets CD38 receptor on the surface of plasma cells and triggers a number of different mechanisms of action to promote apoptosis and regulate the immune response.
the drug was approved by the U.S. FDA in March 2020 to treat adult multiple myeloma patients in association with Pomadamine and ddysemissin.
addition, Sanofi has initiated a number of clinical trials to evaluate the efficacy of isatuximab in combination with different types of standard therapies for patients with multiple myeloma at different stages of the disease.
, Such as Tiandi Bio, Shang Jian Bio and other Chinese companies are also developing at present, China's only Johnson and Johnson's Daleitoyu single resistance to a CD38 mono resistance approved for listing.
but public information shows that there have been a number of CD38 monoanti in China into or about to enter the clinical trial stage, from Sanofi, Tiantian Biological, Shang Jian Biological and other companies.
the progress of CD38 antibody research being developed in China in the following sections.
1, Johnson and Johnson: Darretoyu monoantiodirade was first conditionally approved for marketing in China in July 2019 for the single-drug treatment of adult patients with recurrent and recupgenative multiple myeloma, including patients who had previously received a protease inhibitor and an immunomodant and who developed disease progression during the last treatment, the first CD38 monotherapy to be approved for marketing in China.
July 2020, Johnson and Johnson submitted two new applications for Darretoyu mono-injections in China, meaning the drug is expected to expand new adaptations in China to benefit more patients.
2, Sanofi: Isatuximab Sanofi isatuximab in China has entered phase 3 clinical research phase.
China Drug Clinical Trial Registration and Information Disclosure Platform shows that isatuximab is conducting two clinical trials in China, one of which is a randomized, open international multi-center Phase 3 clinic designed to assess the benefits of the isatuximab joint boronezome, linazolam and dixamisone, compared to boratezomi, linazolamide and tasemison, in extending the new diagnosis of multiple myeloma and not suitable for transplantation of patients without progression survival (PFS).
in July this year, isatuximab obtained two more implied approvals in two clinical trials in China for the use of "combined lysamine and dixamesin for the treatment of high-risk, smoke-producing multiple myeloma (SMM) patients".
3, Sky Creatures: TJ202 TJ202 is a CD38 monoantigen developed by Germany'sMorphoSys, which in 2017 obtained exclusive licensing for the development and commercialization of the drug in Greater China, including Chinese mainland, Hong Kong, Macau and Taiwan.
TJ202 is intended to be developed to treat multiple myeloma and autoimmune diseases, according to the Tiantian Biological Website.
Currently, Tiantian Bio has launched two registered clinical trials in Greater China for the treatment of multiple myeloma patients: an international multi-center Phase 3 clinic designed to evaluate TJ202's combined lysamine and dosemisin The efficacy and safety of the treatment of multiple myeloma, and another is the International Multi-Center Phase 2 clinic, which aims to assess the safety and efficacy of treatment with TJ202 in patients with multiple myeloma who have received at least 2 lines of treatment.
4, Shang jian biological: SG301 SG301 is The anti-CD38 human-sourced monoclonal antibody independently developed by Shang Jian biological, which belongs to the therapeutic biological products category 1.
SG301 identifies new antigen positions and plays a unique role, according to Shang Jian Bio press release.
July 24, SG301's Application for Clinical Trials of New Drugs (IND) was officially accepted by CDE.
the first CHINESE company to independently develop CD38 monoantry, according to a press release from Shangjian Bio.
5, Youzhiyou Biology: Y150 Y150 is an injectable recombinant anti-CD38 and CD3 human-sourced dual-specific antibody product developed using the YBODY® platform technology of Youzhiyou Bio, one end of which targets the highly expressed CD38 antigen of tumor cells and the other end targets the CD3 antigen on the surface of immune T cells.
Y150 recruits T cells to tumor cells by targeting CD38 antigens and CD3 antigens, and activates T cells to kill tumor cells, thereby inhibiting tumor cell growth.
CDE website, Youzhiyou Bio has submitted a clinical trial application for the product in China, which was accepted on July 28.
6: CreditCard Pharmaceuticals: CID-103 CID-103 is a new anti-CD38 monoclonal antibody originally developed by Black Belt Therapeutics, which acquired the exclusive global interest in the drug in April 2019.
according to an earlier press release issued by Kexin Yuanda Pharmaceuticals, CID-103 can kill CD38 plus cell action by activating effect T cells and NK cells.
preclinical studies have shown that CID-103 can induce strong antibody-dependent cytotoxic reactions (ADCC), antibody-dependent intocellular swallowing (ADCP), and complement-dependent cytotoxicity (CDC).
myeloma is the second most common malignant tumor in the blood system, with more than 130,000 newly diagnosed multiple myeloma cases worldwide each year.
although treatments are available, multiple myeloma is still an incurable malignant tumor that most patients recur after treatment or remission.
arrival of CD38 monoantres, providing new options for patients with multiple myeloma, especially those with recurrent and incurable diseases.
expect more breakthroughs in the field of CD38 antibodies for the benefit of more patients.
.