IF 5.3 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-03-27 DOI: 10.1080/19420862.2024.2334783

Jing Xu, John E Coughlin, Malgorzata Szyjka, Serene Jabary, Sonal Saluja, Zoran Sosic, Yunqiu Chen, Chong-Feng Xu

{"title":"Evaluation of the impact of antibody fragments on aggregation of intact molecules via size exclusion chromatography coupled with native mass spectrometry.","authors":"Jing Xu, John E Coughlin, Malgorzata Szyjka, Serene Jabary, Sonal Saluja, Zoran Sosic, Yunqiu Chen, Chong-Feng Xu","doi":"10.1080/19420862.2024.2334783","DOIUrl":"10.1080/19420862.2024.2334783","url":null,"abstract":"Aggregates are recognized as one of the most critical product-related impurities in monoclonal antibody (mAb)-based therapeutics due to their negative impact on the stability and safety of the drugs. So far, investigational efforts have primarily focused on understanding the causes and effects of mAb self-aggregation, including both internal and external factors. In this study, we focused on understanding mAb stability in the presence of its monovalent fragment, formed through hinge cleavage and loss of one Fab unit (referred to as \"Fab/c\"), a commonly observed impurity during manufacturing and stability. The Fab/c fragments were generated using a limited IgdE digestion that specifically cleaves above the IgG1 mAb hinge region, followed by hydrophobic interaction chromatographic (HIC) enrichment. Two IgG1 mAbs containing different levels of Fab/c fragments were incubated under thermally accelerated conditions. A method based on size exclusion chromatography coupled with native mass spectrometry (SEC-UV-native MS) was developed and used to characterize the stability samples and identified the formation of heterogeneous dimers, including intact dimer, mAb-Fab/c dimer, Fab/c-Fab/c dimer, and mAb-Fab dimer. Quantitative analyses on the aggregation kinetics suggested that the impact of Fab/c fragment on the aggregation rate of individual dimer differs between a glycosylated mAb (mAb1) and a non-glycosylated mAb (mAb2). An additional study of deglycosylated mAb1 under 25°C accelerated stability conditions suggests no significant impact of the N-glycan on mAb1 total aggregation rate. This study also highlighted the power of SEC-UV-native MS method in the characterization of mAb samples with regard to separating, identifying, and quantifying mAb aggregates and fragments.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2334783"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of the bispecific VHH antibody tarperprumig (ALXN1820) specific for properdin and designed for low-volume administration. 针对 properdin 的特异性双特异性 VHH 抗体 tarperprumig（ALXN1820）的特性分析，该抗体专为小剂量给药而设计。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-10-13 DOI: 10.1080/19420862.2024.2415060

Paul Tamburini, Dennis Vestergaard Pedersen, Denise Devore, Josh Cone, Rekha Patel, Todd Hunter, Fang Sun, Gregers Rom Andersen, Jeffrey Hunter

{"title":"Characterization of the bispecific VHH antibody tarperprumig (ALXN1820) specific for properdin and designed for low-volume administration.","authors":"Paul Tamburini, Dennis Vestergaard Pedersen, Denise Devore, Josh Cone, Rekha Patel, Todd Hunter, Fang Sun, Gregers Rom Andersen, Jeffrey Hunter","doi":"10.1080/19420862.2024.2415060","DOIUrl":"https://doi.org/10.1080/19420862.2024.2415060","url":null,"abstract":"The bispecific antibody tarperprumig (ALXN1820) was developed as a treatment option for diseases involving dysregulated complement alternative pathway (AP) activity that could be administered in small volumes, either subcutaneously or intravenously. Tarperprumig incorporates a C-terminal variable domain of a heavy chain only antibody (VHH) that binds properdin (FP) connected via a flexible linker to an N-terminal VHH that binds human serum albumin (HSA). The purified bispecific VHH antibody exhibits an experimental molecular weight average of 27.4 kDa and can be formulated at > 100 mg/mL. Tarperprumig binds tightly to FP and HSA with sub-nanomolar affinity at pH 7.4 and can associate simultaneously with FP and HSA to form a ternary complex. Tarperprumig potently and dose-dependently inhibits to completion in vitro AP-dependent complement C5b-9 formation, AP-dependent hemolysis, and the AP deposition of C3, FP and C9. X-ray crystallography revealed that the isolated FP-binding VHH recognizes the thrombospondin repeat 5 domain of FP, thereby preventing FP from binding to the AP convertase owing to severe steric hindrance. Tarperprumig cross-reacts with cynomolgus monkey FP and serum albumin. In summary, tarperprumig exhibits properties tailored for subcutaneous administration and is currently in clinical development for the treatment of complement AP-related disorders.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2415060"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The emergence of cell-based protein arrays to test for polyspecific off-target binding of antibody therapeutics. 基于细胞的蛋白质阵列用于检测抗体疗法的多特异性脱靶结合。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-08-24 DOI: 10.1080/19420862.2024.2393785

Diana M Norden, Carmen T Navia, Jonathan T Sullivan, Benjamin J Doranz

{"title":"The emergence of cell-based protein arrays to test for polyspecific off-target binding of antibody therapeutics.","authors":"Diana M Norden, Carmen T Navia, Jonathan T Sullivan, Benjamin J Doranz","doi":"10.1080/19420862.2024.2393785","DOIUrl":"10.1080/19420862.2024.2393785","url":null,"abstract":"Specificity profiling is a requirement for monoclonal antibodies (mAbs) and antibody-directed biotherapeutics such as CAR-T cells prior to initiating human trials. However, traditional approaches to assess the specificity of mAbs, primarily tissue cross-reactivity studies, have been unreliable, leading to off-target binding going undetected. Here, we review the emergence of cell-based protein arrays as an alternative and improved assessment of mAb specificity. Cell-based protein arrays assess binding across the full human membrane proteome, ~6,000 membrane proteins each individually expressed in their native structural configuration within live or unfixed cells. Our own profiling indicates a surprisingly high off-target rate across the industry, with 33% of lead candidates displaying off-target binding. Moreover, about 20% of therapeutic mAbs in clinical development and currently on the market display off-target binding. Case studies and off-target rates at different phases of biotherapeutic drug approval suggest that off-target binding is likely a major cause of adverse events and drug attrition.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2393785"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability. 下一代 Fab 库平台可直接产生具有高亲和力、多样性和可开发性的类药物抗体。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-08-27 DOI: 10.1080/19420862.2024.2394230

Fortunato Ferrara, Adeline Fanni, Andre A R Teixeira, Esteban Molina, Camila Leal-Lopes, Ashley DeAguero, Sara D'Angelo, M Frank Erasmus, Laura Spector, Luis Antonio Rodriguez Carnero, Jianquan Li, Thomas J Pohl, Nikolai Suslov, Klervi Desrumeaux, Conor McMahon, Sagar Kathuria, Andrew R M Bradbury

{"title":"A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability.","authors":"Fortunato Ferrara, Adeline Fanni, Andre A R Teixeira, Esteban Molina, Camila Leal-Lopes, Ashley DeAguero, Sara D'Angelo, M Frank Erasmus, Laura Spector, Luis Antonio Rodriguez Carnero, Jianquan Li, Thomas J Pohl, Nikolai Suslov, Klervi Desrumeaux, Conor McMahon, Sagar Kathuria, Andrew R M Bradbury","doi":"10.1080/19420862.2024.2394230","DOIUrl":"10.1080/19420862.2024.2394230","url":null,"abstract":"We previously described an in vitro single-chain fragment (scFv) library platform originally designed to generate antibodies with excellent developability properties. The platform design was based on the use of clinical antibodies as scaffolds into which replicated natural complementarity-determining regions purged of sequence liabilities were inserted, and the use of phage and yeast display to carry out antibody selection. In addition to being developable, antibodies generated using our platform were extremely diverse, with most campaigns yielding sub-nanomolar binders. Here, we describe a platform advancement that incorporates Fab phage display followed by single-chain antibody-binding fragment Fab (scFab) yeast display. The scFab single-gene format provides balanced expression of light and heavy chains, with enhanced conversion to IgG, thereby combining the advantages of scFvs and Fabs. A meticulously engineered, quality-controlled Fab phage library was created using design principles similar to those used to create the scFv library. A diverse panel of binding scFabs, with high conversion efficiency to IgG, was isolated against two targets. This study highlights the compatibility of phage and yeast display with a Fab semi-synthetic library design, offering an efficient approach to generate drug-like antibodies directly, facilitating their conversion to potential therapeutic candidates.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2394230"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coactivation of Tie2 and Wnt signaling using an antibody-R-spondin fusion potentiates therapeutic angiogenesis and vessel stabilization in hindlimb ischemia. 使用抗体-R-软骨素融合体共同激活 Tie2 和 Wnt 信号，可增强后肢缺血时的治疗性血管生成和血管稳定。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-11-28 DOI: 10.1080/19420862.2024.2435478

Byungtae Hwang, Min-Young Jeon, Ju-Hong Jang, Young-Lai Cho, Dong Gwang Lee, Jeong-Ki Min, Jangwook Lee, Jong-Gil Park, Ji-Hun Noh, Wonjun Yang, Nam-Kyung Lee

{"title":"Coactivation of Tie2 and Wnt signaling using an antibody-R-spondin fusion potentiates therapeutic angiogenesis and vessel stabilization in hindlimb ischemia.","authors":"Byungtae Hwang, Min-Young Jeon, Ju-Hong Jang, Young-Lai Cho, Dong Gwang Lee, Jeong-Ki Min, Jangwook Lee, Jong-Gil Park, Ji-Hun Noh, Wonjun Yang, Nam-Kyung Lee","doi":"10.1080/19420862.2024.2435478","DOIUrl":"10.1080/19420862.2024.2435478","url":null,"abstract":"Therapeutic angiogenesis by intentional formation of blood vessels is essential for treating various ischemic diseases, including limb ischemia. Because Wnt/β-catenin and angiopoietin-1/Tie2 signaling play important roles in endothelial survival and vascular stability, coactivation of these signaling pathways can potentially achieve therapeutic angiogenesis. In this study, we developed a bifunctional antibody fusion, consisting of a Tie2-agonistic antibody and the Furin domains of R-spondin 3 (RSPO3), to simultaneously activate Tie2 and Wnt/β-catenin signaling. We identified a Tie2-agonistic antibody T11 that cross-reacted with the extracellular domain of human and mouse Tie2, and evaluated its ability to increase endothelial cell survival and tube formation. We generated a bifunctional T11-RF12 by fusing T11 with the Furin-1 and -2 domains of RSPO3. T11-RF12 could bind not only to Tie2, but also to LGR5 and ZNRF3, which are counterparts of the Furin-1 and -2 domains. T11-RF12 significantly increased Wnt/β-catenin signaling, as well as the formation of capillary-like endothelial tubes, regardless of the presence of Wnt ligands. Coactivation of Tie2 and Wnt/β-catenin signaling by T11-RF12 increased the blood flow, and thereby reduced foot necrosis in a mouse hindlimb ischemia model. In particular, T11-RF12 induced therapeutic angiogenesis by promoting vessel stabilization through pericyte coverage and retaining endothelial expression of Frizzled 10 and active β-catenin. These results indicate that the agonistic synergism of Tie2 and Wnt/β-catenin signaling achieved using T11-RF12 is a novel therapeutic option with potential for treating limb ischemia and other ischemic diseases.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2435478"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 更正。

IF 5.3 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-05-12 DOI: 10.1080/19420862.2024.2354626

引用次数: 0

Structural analysis of light chain-driven bispecific antibodies targeting CD47 and PD-L1. 针对 CD47 和 PD-L1 的轻链驱动双特异性抗体的结构分析。

IF 5.3 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-06-07 DOI: 10.1080/19420862.2024.2362432

Pauline Malinge, Xavier Chauchet, Jérémie Bourguignon, Nicolas Bosson, Sébastien Calloud, Tereza Bautzova, Marie Borlet, Mette Laursen, Vinardas Kelpsas, Nadia Rose, Franck Gueneau, Ulla Ravn, Giovanni Magistrelli, Nicolas Fischer

{"title":"Structural analysis of light chain-driven bispecific antibodies targeting CD47 and PD-L1.","authors":"Pauline Malinge, Xavier Chauchet, Jérémie Bourguignon, Nicolas Bosson, Sébastien Calloud, Tereza Bautzova, Marie Borlet, Mette Laursen, Vinardas Kelpsas, Nadia Rose, Franck Gueneau, Ulla Ravn, Giovanni Magistrelli, Nicolas Fischer","doi":"10.1080/19420862.2024.2362432","DOIUrl":"10.1080/19420862.2024.2362432","url":null,"abstract":"In contrast to natural antibodies that rely mainly on the heavy chain to establish contacts with their cognate antigen, we have developed a bispecific antibody format in which the light chain (LC) drives antigen binding and specificity. To better understand epitope-paratope interactions in this context, we determined the X-ray crystallographic structures of an antigen binding fragment (Fab) in complex with human CD47 and another Fab in complex with human PD-L1. These Fabs contain a κ-LC and a λ-LC, respectively, which are paired with an identical heavy chain (HC). The structural analysis of these complexes revealed the dominant contribution of the LCs to antigen binding, but also that the common HC provides some contacts in both CD47 and PD-L1 Fab complexes. The anti-CD47 Fab was affinity optimized by diversifying complementary-determining regions of the LC followed by phage display selections. Using homology modeling, the contributions of the amino acid modification to the affinity increase were analyzed. Our results demonstrate that, despite a less prominent role in natural antibodies, the LC can mediate high affinity binding to different antigens and neutralize their biological function. Importantly, Fabs containing a common variable heavy (VH) domain enable the generation of bispecific antibodies retaining a truly native structure, maximizing their therapeutic potential.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2362432"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of the high concentration viscosity of IgG₁ antibodies using clinically validated Fc mutations. 利用临床验证的 Fc 突变调节 IgG1 抗体的高浓度粘度。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-07-19 DOI: 10.1080/19420862.2024.2379560

Joel Heisler, Daniel Kovner, Saeed Izadi, Jonathan Zarzar, Paul J Carter

{"title":"Modulation of the high concentration viscosity of IgG1 antibodies using clinically validated Fc mutations.","authors":"Joel Heisler, Daniel Kovner, Saeed Izadi, Jonathan Zarzar, Paul J Carter","doi":"10.1080/19420862.2024.2379560","DOIUrl":"10.1080/19420862.2024.2379560","url":null,"abstract":"The self-association of therapeutic antibodies can result in elevated viscosity and create problems in manufacturing and formulation, as well as limit delivery by subcutaneous injection. The high concentration viscosity of some antibodies has been reduced by variable domain mutations or by the addition of formulation excipients. In contrast, the impact of Fc mutations on antibody viscosity has been minimally explored. Here, we studied the effect of a panel of common and clinically validated Fc mutations on the viscosity of two closely related humanized IgG1, κ antibodies, omalizumab (anti-IgE) and trastuzumab (anti-HER2). Data presented here suggest that both Fab-Fab and Fab-Fc interactions contribute to the high viscosity of omalizumab, in a four-contact model of self-association. Most strikingly, the high viscosity of omalizumab (176 cP) was reduced 10.7- and 2.2-fold by Fc modifications for half-life extension (M252Y:S254T:T256E) and aglycosylation (N297G), respectively. Related single mutations (S254T and T256E) each reduced the viscosity of omalizumab by ~6-fold. An alternative half-life extension Fc mutant (M428L:N434S) had the opposite effect in increasing the viscosity of omalizumab by 1.5-fold. The low viscosity of trastuzumab (8.6 cP) was unchanged or increased by <math><mo>≤</mo></math>2-fold by the different Fc variants. Molecular dynamics simulations provided mechanistic insight into the impact of Fc mutations in modulating electrostatic and hydrophobic surface properties as well as conformational stability of the Fc. This study demonstrates that high viscosity of some IgG1 antibodies can be mitigated by Fc mutations, and thereby offers an additional tool to help design future antibody therapeutics potentially suitable for subcutaneous delivery.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2379560"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery and development of ANV419, an IL-2/anti-IL-2 antibody fusion protein with potent CD8+ T and natural killer cell-stimulating capacity for cancer immunotherapy. 发现并开发用于癌症免疫疗法的 IL-2/anti-IL-2 抗体融合蛋白 ANV419，它具有强大的 CD8+ T 细胞和自然杀伤细胞刺激能力。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-07-23 DOI: 10.1080/19420862.2024.2381891

Patrizia Murer, Barbara Brannetti, Jean-Michel Rondeau, Laetitia Petersen, Nicole Egli, Simone Popp, Catherine Regnier, Kirsten Richter, Andreas Katopodis, Christoph Huber

{"title":"Discovery and development of ANV419, an IL-2/anti-IL-2 antibody fusion protein with potent CD8+ T and natural killer cell-stimulating capacity for cancer immunotherapy.","authors":"Patrizia Murer, Barbara Brannetti, Jean-Michel Rondeau, Laetitia Petersen, Nicole Egli, Simone Popp, Catherine Regnier, Kirsten Richter, Andreas Katopodis, Christoph Huber","doi":"10.1080/19420862.2024.2381891","DOIUrl":"10.1080/19420862.2024.2381891","url":null,"abstract":"Novel engineered IL-2 agonists strive to increase the therapeutic window of aldesleukin (human IL-2) by increasing selectivity toward effector over regulatory T cells and reducing dose-limiting toxicities. Here we describe ANV419, an IL-2/anti-IL2 antibody fusion protein designed for selective IL-2 receptor βγ (IL-2 Rβγ) activation by sterically hindering IL-2 from binding to IL-2 Rα. The fusion protein has an IL-2 connected to the light chain complementarity-determining region (CDR) domain of a humanized antibody that binds to IL-2 at the same epitope as IL-2 Rα. Optimization of the selectivity and pharmacological properties led to the selection of ANV419. ANV419 preferentially expands CD8+ T cells and natural killer (NK) cells over Tregs and can be safely administered at doses that elicit strong pharmacodynamic effects and efficacy in mouse tumor models. Its anti-tumor efficacy was enhanced when combined with programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors. ANV419 also enhances the NK cell killing capacity and increases tumor growth inhibition when used alongside trastuzumab in a Her-2+ xenograft mouse model. In cynomolgus monkeys, the estimated half-life of ANV419 is 24 h, and doses that induced sustained expansion of effector cells were well tolerated without the severe toxicities typically observed with high-dose IL-2. These data support the clinical development of ANV419 in solid tumors and hematological malignancies as monotherapy and in combination with checkpoint inhibitors or agents that induce antibody-dependent cellular cytotoxicity. ANV419 is currently in Phase 1/2 clinical development and may provide cancer patients with a wider therapeutic window than aldesleukin.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2381891"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Agonistic anti-NKG2D antibody structure reveals unique stoichiometry and epitope compared to natural ligands. 与天然配体相比，激动型抗 NKG2D 抗体结构揭示了独特的化学计量学和表位。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-11-25 DOI: 10.1080/19420862.2024.2433121

Daniel Fallon, Ching-Shin Huang, Jingya Ma, Christopher Morgan, Zhaohui Sunny Zhou

引用次数: 0

mAbs最新文献