Mupadolimab
(Synonyms: CPI-006) 目录号 : GC68344Mupadolimab (CPI-006) 是一种 IgG1κ 人源化的 FcγR 结合缺陷抗 CD73 单抗,激活 CD73POS B 细胞。
Cas No.:2451856-97-4
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Mupadolimab (CPI-006) is an IgG1κ humanized FcγR binding-deficient anti-CD73 monoclonal antibody (mAb) that activates CD73POS B cells[1].
Mupadolimab induces the increased expression of markers associated with B cell maturation and antigen presentation, morphologic transformation to plasmablasts, and increased secretion of IgM and IgG[1].
Mupadolimab (10 mg/kg; i.p.; daily for 15 days) stimulates antigen specific humoral immunity in SARS-CoV-2 infected NSG-SGM3 mice[1].
Animal Model: | NSG-SGM3 mice, immunized with an emulsion of 50 μg full length spike protein from SARS-CoV-2 and Freund's Incomplete Adjuvant subcutaneously on both the left and right flank (25 μg/side)[1] |
Dosage: | 10 mg/kg |
Administration: | Intraperitoneal injection, daily for 15 days |
Result: | Mice treated with the drug made antibodies to the immunizing TS protein; but not to the control nucleocapsid SARS-CoV-2 viral protein. |
[1]. Miller R A, et al. Clinical results with a B cell activating anti-CD73 antibody for the immunotherapy of Covid-19. medRxiv, 2021.
Cas No. | 2451856-97-4 | SDF | Download SDF |
别名 | CPI-006 | ||
分子式 | 分子量 | ||
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Anti-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer
J Immunother Cancer 2022 Dec;10(12):e005802.PMID:36600561DOI:PMC9723961
Background: CD73 is widely expressed on immune cells playing a critical role in immunomodulatory functions including cell adhesion and migration, as a costimulatory molecule for T cells and in production of adenosine. The function of CD73 expressed on B cells has not been fully characterized. Mupadolimab is an anti-human CD73 antibody that activates B cells. We evaluated the characteristics of this antibody and its effects on immune cells in vitro and in vivo. Methods: Mupadolimab binding to CD73, inhibition of CD73 enzymatic activity, and effects on lymphocyte activation were evaluated in vitro by measuring changes in immunophenotype by flow cytometry. Cryogenic-transmission electron microscopy was used to determine epitope binding. Effects on human B cells in vivo were evaluated in immunodeficient NSG-SGM3 mice immunized with SARS-CoV-2 and influenza viral antigens. Safety and immune effects were evaluated in the completed dose escalation portion of a phase 1 trial conducted in patients with cancer. Results: Mupadolimab binds to a unique epitope on CD73POS B cells resulting in their activation and differentiation through B cell receptor signaling pathways. Mupadolimab induces expression of CD69, CD83, CD86 and MHC class II on B cells along with morphological transformation into plasmablasts and expression of CD27, CD38 and CD138. These effects are independent of adenosine. Mupadolimab binds to the N-terminal of CD73 in the closed position and competitively inhibits substrate binding. Mupadolimab enhanced antigen specific antibody response to SARS-CoV-2 spike protein and influenza hemagglutinin in humanized mouse models. Mupadolimab was evaluated as a monotherapy in a phase 1 trial (NCT03454451) in 34 patients with advanced cancer and demonstrated binding to CD73POS circulating cells and transient reduction in the number of B cells, with return of CD73NEG B cells with memory phenotype. No dose-limiting toxicities or changes in serum immunoglobulins were seen. Conclusions: Mupadolimab activates B cells and stimulates the production of antigen specific antibodies. The effects in patients with cancer suggest that activated, CD69POS B cells redistribute to lymphoid tissues. Minor tumor regression was observed in several patients. These results support further investigation of Mupadolimab as an immunotherapy for cancer and its potential use as a vaccine adjuvant. Trial registration number: NCT03454451.