Luigi Grasso, Bradford J Kline, Nicholas C Nicolaides
{"title":"通过重组利妥昔单抗（NAV-006）绕过CA125/MUC16的免疫抑制作用，提高其体内抗肿瘤活性。","authors":"Luigi Grasso, Bradford J Kline, Nicholas C Nicolaides","doi":"10.1093/abt/tbaf008","DOIUrl":null,"url":null,"abstract":"<p><p>The monoclonal antibody rituximab functions through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) and is used to treat non-Hodgkin's lymphoma. Elevated serum CA125/MUC16 levels, present in some follicular lymphoma patients, have been shown to correlate with reduced efficacy of rituximab. Previous studies revealed that CA125/MUC16 binds to rituximab, diminishing its CDC and ADCC. A rituximab variant, NAV-006, was engineered to counteract CA125/MUC16's immunosuppressive effects. NAV-006 demonstrated enhanced CDC and ADCC activities and was unaffected by CA125/MUC16. In the present study, NAV-006 showed improved <i>in vivo</i> antitumor activity compared to rituximab in a human lymphoma model with reconstituted CA125/MUC16. Additionally, CA125/MUC16 bound to newer antibody-based lymphoma treatment agents, including obinutuzumab and tafasitamab, suppressing their immune effector functions. Bispecific antibodies mosunetuzumab and glofitamab also exhibited reduced cytotoxicity in the presence of CA125/MUC16. These findings suggest that NAV-006 could improve therapeutic efficacy in B-cell lymphomas, particularly in patients with elevated CA125/MUC16 levels.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"171-176"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199351/pdf/","citationCount":"0","resultStr":"{\"title\":\"Bypassing the immunosuppressive effects of CA125/MUC16 via re-engineered rituximab (NAV-006) to improve its antitumor activity <i>in vivo</i>.\",\"authors\":\"Luigi Grasso, Bradford J Kline, Nicholas C Nicolaides\",\"doi\":\"10.1093/abt/tbaf008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The monoclonal antibody rituximab functions through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) and is used to treat non-Hodgkin's lymphoma. Elevated serum CA125/MUC16 levels, present in some follicular lymphoma patients, have been shown to correlate with reduced efficacy of rituximab. Previous studies revealed that CA125/MUC16 binds to rituximab, diminishing its CDC and ADCC. A rituximab variant, NAV-006, was engineered to counteract CA125/MUC16's immunosuppressive effects. NAV-006 demonstrated enhanced CDC and ADCC activities and was unaffected by CA125/MUC16. In the present study, NAV-006 showed improved <i>in vivo</i> antitumor activity compared to rituximab in a human lymphoma model with reconstituted CA125/MUC16. Additionally, CA125/MUC16 bound to newer antibody-based lymphoma treatment agents, including obinutuzumab and tafasitamab, suppressing their immune effector functions. Bispecific antibodies mosunetuzumab and glofitamab also exhibited reduced cytotoxicity in the presence of CA125/MUC16. These findings suggest that NAV-006 could improve therapeutic efficacy in B-cell lymphomas, particularly in patients with elevated CA125/MUC16 levels.</p>\",\"PeriodicalId\":36655,\"journal\":{\"name\":\"Antibody Therapeutics\",\"volume\":\"8 3\",\"pages\":\"171-176\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199351/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antibody Therapeutics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/abt/tbaf008\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antibody Therapeutics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/abt/tbaf008","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Bypassing the immunosuppressive effects of CA125/MUC16 via re-engineered rituximab (NAV-006) to improve its antitumor activity in vivo.
The monoclonal antibody rituximab functions through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) and is used to treat non-Hodgkin's lymphoma. Elevated serum CA125/MUC16 levels, present in some follicular lymphoma patients, have been shown to correlate with reduced efficacy of rituximab. Previous studies revealed that CA125/MUC16 binds to rituximab, diminishing its CDC and ADCC. A rituximab variant, NAV-006, was engineered to counteract CA125/MUC16's immunosuppressive effects. NAV-006 demonstrated enhanced CDC and ADCC activities and was unaffected by CA125/MUC16. In the present study, NAV-006 showed improved in vivo antitumor activity compared to rituximab in a human lymphoma model with reconstituted CA125/MUC16. Additionally, CA125/MUC16 bound to newer antibody-based lymphoma treatment agents, including obinutuzumab and tafasitamab, suppressing their immune effector functions. Bispecific antibodies mosunetuzumab and glofitamab also exhibited reduced cytotoxicity in the presence of CA125/MUC16. These findings suggest that NAV-006 could improve therapeutic efficacy in B-cell lymphomas, particularly in patients with elevated CA125/MUC16 levels.
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