▎Edited by the WuXi AppTec content teamThe official website of the Center for Drug Evaluation (CDE) under the China National Medical Products Administration announced that JNJ-80948543 Injection, a Class 1 new drug from Johnson & Johnson Innovative Medicine, a subsidiary of Johnson & Johnson, has been approved for clinical trials, intended for development in treatment.Malignant Lymphoma. Public information shows that this is aNew TypeCD79b x CD20 x CD3 TrispecificT Cell RedirectionAntibody。Screenshot source: CDE official websiteResearch has found that for relapsed/refractory lymphoid malignancies, T-cell redirection using antibodies that recognize CD3 on T cells and specific antigens on malignant cells is a promising treatment approach, potentially helping patients who no longer respond to frontline therapies.Compared with bispecific antibodies, trispecific antibodies targeting two tumor antigens can further enhance the efficacy of CD3 redirection therapy.CD79b and CD20 are both well-validated therapeutic targets, with expression restricted to the B-cell lineage and present in most B-cell malignancies, making them ideal T-cell redirecting targets for B lymphocyte malignancies.According to public information from Johnson & Johnson, JNJ-80948543 isIs a trispecificT Cell RedirectionAntibody,ItCan bind to CD3 antigen on T cells and CD79b and CD20 on B cells, leading to the lysis of malignant B cells.. AndBispecificCompared with antibodies,TrispecificAntibodies canEnhanced affinity to boost potency and maximize tumor eradication in the presence of non-homologous cell populations, thereby improving therapeutic outcomes.
▲Schematic diagram of the mechanism of action of JNJ-80948543. (Screenshot source: Reference [3])
According to the publication inBloodA paper published in a journal reported that JNJ-80948543 can exhibit performance in lymphoma cells expressing different endogenous CD79b and CD20 receptor densities.High Affinity, Stable Binding, and with primary human T cells expressing CD3Low-affinity bindingIn vitro studies have shown that JNJ-80948543 exhibits cytotoxicity in a broad panel of lymphoma cell lines and primary B cells, with observed T-cell activation and low cytokine secretion. Additionally, JNJ-80948543 mediates cytotoxicity in tumor cells expressing either CD79b or CD20 single targets, while demonstrating >1000-fold potency in cells co-expressing CD79b and CD20. In vivo studies have shown,JNJ-80948543 inhibits the growth of CARNAVAL (GCB-DLBCL) xenograft tumors and induces dose-dependent regression of OCI-Ly10 (ABC-DLBCL) xenograft tumors.。ClinicalTrialsThe official website information shows that Johnson & Johnson Innovative Medicine is conducting two Phase 1 clinical studies on JNJ-80948543: one is to evaluate the safety of JNJ-80948543 in subjects with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), aiming to confirm the recommended Phase 2 dose (RP2D) and optimal dosing regimen; the other isPhase 2 Clinical Study, Aiming toEvaluation of JNJ-80948543Combination T-cell Engager Therapy for B-cell NHLSubject's.The granting of clinical trial implied permission for this product in China means that it will also commence clinical research in China. We hope the subsequent development of this drug proceeds smoothly and achieves positive results, benefiting a wide range of patients as soon as possible.References:
[1] Official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.Retrieved Mar 6, 2024, from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
[2] Balendran, S.,Tam, C., Ku, M. (2023) T-Cell Engaging Antibodies in Diffuse Large B Cell
Lymphoma—An Update. J. Clin. Med. https://www.mdpi.com/2077-0383/12/21/6737
[3] Anna Kuchnio, Danlin Yang, Nele
Vloemans, et al. (2022) Characterization of JNJ-80948543, a Novel
CD79bxCD20xCD3 Trispecific T-Cell Redirecting Antibody for the Treatment of
B-Cell Non-Hodgkin Lymphoma. Blood. https://ashpublications.org/blood/article/140/Supplement%201/3105/488652/Characterization-of-JNJ-80948543-a-Novel
[4] A Study of JNJ-80948543, a T-cell Redirecting CD79b x CD20 x CD3 Trispecific Antibody, in Participants With Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). From https://globaltrialfinder.janssen.com/trial/CR109174
This article is from the content team of WuXi AppTec. Individuals are welcome to share it on their social media feeds, but unauthorized reprints by media or organizations in any form to other platforms are prohibited. For reprint authorization, please leave a message on the "MedView" WeChat Official Account to contact us. For other collaboration inquiries, please contact wuxi_media@wuxiapptec.com.
Disclaimer: The content team of WuXi AppTec focuses on introducing the research progress in global biomedicine and health. This article is for information exchange only, and the views expressed in the article do not represent the position of WuXi AppTec, nor does it imply that WuXi AppTec supports or opposes these views. This article is not a recommendation for treatment plans. For guidance on treatment options, please visit a正规 hospital.
