Antibody Therapeutics最新文献

{"title":"POTENT AND SELECTIVE A2AR MONOCLONAL ANTIBODY ANTAGONIST FOR THE TREATMENT OF CANCER","authors":"Changyun Hu, Yanyan Wang, Xiqian Lan, Jiandong Zhang, Xinyan Zhao","doi":"10.1093/abt/tbad014.010","DOIUrl":"https://doi.org/10.1093/abt/tbad014.010","url":null,"abstract":"Abstract Background and significance The presence of adenosine at abnormally high concentrations in tumor microenvironment leads to the activation of adenosine receptor 2A (A2aR) and represents one of the mechanisms for cancer patients to be resistance to immune checkpoint blockade therapies. CD39 and CD73 play an important role in converting ATP to adenosine. Currently antibodies or small molecule inhibitors (SMIs) targeting CD39 and CD73, as well as SMIs targeting adenosine receptors, are under preclinical investigation and early clinical development. However, effective biologics targeting adenosine receptors has not been reported. Here we demonstrated that humanized anti-A2aR antibodies represent promising novel therapeutic candidates for developing immunotherapy to restore anti-tumor responses in solid tumors that only partially respond or are completely resistance to ICB therapies. Methods Humanized anti-human A2aR monoclonal antibodies (mAbs) were generated from mouse hybridoma antibody via classic CDR grafting method. The A2aR binding and non-human primate cross-reactivity were measured by FACS using human A2aR-expressing HEK293 cells as well as human and cynomolgus monkey PBMCs. Internalizing properties were determined by FACS and immunofluorescent method. The cellular potency of these mAbs was assessed by their capability of inhibiting cAMP production induced by A2aR agonist adenosine and NECA in hA2aR-overexpressing HEK293 cells. The ability of lead candidates to reverse adenosine-mediated suppression of human effector cell function was determined using standard CD3/CD28 activation conditions in the presence of A2aR agonist NECA. Results and Conclusion We successfully humanized anti-A2aR antibody discovered via hybridoma technology. Humanized anti-A2aR antibodies maintain binding, cross-reactivity to human and cynomolgus monkey A2aR, as well as internalizing property and A2aR-antagonizing potency, in comparison with parental antibody. Humanized antibodies are 5~10 fold more potent than clinical stage small molecule inhibitors CPI-444 and AB928 in inhibiting cAMP production. Blockade of A2aR with humanized antibody can restore activation and cytokine production of human T and NK cells suppressed by A2aR agonist adenosine or NECA. Thus, antibody-mediated blockade of A2aR pathway represents a novel strategy to mitigate adenosine-mediated tumor resistance to immune checkpoint blockade therapies.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43810777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRELIMINARY SAFETY, EFFICACY AND PHARMACOKINETICS (PK) RESULTS OF KN026 (A HER2 BISPECIFIC ANTIBODY) MONOTHERAPY IN ADVANCED SOLID TUMOR PATIENTS WITH HER2 EXPRESSION","authors":"T. Xu, Yuan-Fei Lv, Jie Sun, Jianjian Peng, Jingqiu Li, Xionghui Li, B. Guo","doi":"10.1093/abt/tbad014.006","DOIUrl":"https://doi.org/10.1093/abt/tbad014.006","url":null,"abstract":"Abstract Background KN026 is a novel bispecific antibody and simultaneously binds to two distinct HER2 epitopes which are the same domains as trastuzumab (ECD4) and pertuzumab (ECD2). It showed higher maximal binding than monospecific HER2 antibodies and favors that crosslinking of HER2 receptors could enhance the receptors internalization in preclinical studies. KN026 significantly inhibited the growth of human cancer cell lines and demonstrated obviously antitumor activity against different xenografts models. The encouraging efficacy and manageable safety of KN026 were reported in Chinese cancer patients (pts) with HER2 expression and ph3 study is ongoing in gastric cancer (NCT05427383). Methods The late line solid tumor pts with HER2 expression who were refractory to or ineligible for standard therapy were recruited in this phase I dose-escalation study in US (NCT03847168). All pts intravenously received KN026 monotherapy at ascending dose of 10 mg/kg (QW), 20 mg/kg (Q2W) or 30 mg/kg (Q3W). Dose escalation followed standard “3 + 3” design. Expansion was determined by Safety Monitoring Committee (SMC). The primary objectives were to evaluate safety and tolerability of KN026 and determine the MTD and/or RP2D. Safety was evaluated according to CTCAE v 5.0, and efficacy was assessed by RECIST 1.1. Results A total of 22 pts with median 4 lines prior treatment were enrolled, including 5 breast cancer pts, 3 gastric or gastroesophageal junction cancer pts and 14 other solid tumor pts. 21 pts were included in the efficacy analysis. The median age was 57.0 (47-79), with 8 males and 14 females and most of pts were Caucasian (72.7%). 3, 10 (7 at expansion phase), and 9 (6 at expansion phase) pts were treated at 10mg/kg, 20mg/kg, 30mg/kg, respectively. No dose-limiting toxicities (DLTs) were observed and MTD wasn’t reached. 20 pts (90.9%) occurred TRAEs and the common (≥20%) TRAEs were diarrhea (45.5%), fatigue (40.9%), chills (36.4%) and nausea (27.3%). Most of TRAE were Gr 1-2, and only 3 pts (13.6%) experienced ≥ Gr3 TRAE (anemia, fatigue and pneumonitis) without treatment discontinuation and death caused by KN026. 4 of 21 pts (1 at 10mg/kg, 2 at 20 mg/kg, 1 at 30mg/kg) achieved objective response (ORR 19.0%, 95% CI: 5.5, 41.9), and DCR was 61.9% (95% CI: 38.4, 81.9). The exposure of KN026 and T1/2 increased with dose escalation. Accumulation ratio of Cmax and AUC was 1.18-1.42 and 1.14-1.71. The concentration of Ctrough was over 20μM at all dose levels. There was only one positive ADA sample in 20 mg/kg group in C1D1. And the RP2D was 20mg/kg Q2W or 30mg/kg Q3W. Conclusion KN026 was well tolerated and showed the promising anti-tumor activity in US pts with HER2 expression. Besides, KN026 has well pharmacokinetic profile and favorable immunogenicity.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42160602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mammalian cell display platform based on scFab transposition.","authors":"Jing Chang, Christoph Rader, Haiyong Peng","doi":"10.1093/abt/tbad009","DOIUrl":"10.1093/abt/tbad009","url":null,"abstract":"<p><p><i>In vitro</i> display technologies have been successfully utilized for the discovery and evolution of monoclonal antibodies (mAbs) for diagnostic and therapeutic applications, with phage display and yeast display being the most commonly used platforms due to their simplicity and high efficiency. As their prokaryotic or lower eukaryotic host organisms typically have no or different post-translational modifications, several mammalian cell-based display and screening technologies for isolation and optimization of mAbs have emerged and are being developed. We report here a novel and useful mammalian cell display platform based on the PiggyBac transposon system to display mAbs in a single-chain Fab (scFab) format on the surface of HEK293F cells. Immune rabbit antibody libraries encompassing ~7 × 10⁷ independent clones were generated in an all-in-one transposon vector, stably delivered into HEK293F cells and displayed as an scFab with rabbit variable and human constant domains. After one round of magnetic activated cell sorting and two rounds of fluorescence activated cell sorting, mAbs with high affinity in the subnanomolar range and cross-reactivity to the corresponding human and mouse antigens were identified, demonstrating the power of this platform for antibody discovery. We developed a highly efficient mammalian cell display platform based on the PiggyBac transposon system for antibody discovery, which could be further utilized for humanization as well as affinity and specificity maturation.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9878127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TransMHCII: a novel MHC-II binding prediction model built using a protein language model and an image classifier.","authors":"Xin Yu, Christopher Negron, Lili Huang, Geertruida Veldman","doi":"10.1093/abt/tbad011","DOIUrl":"10.1093/abt/tbad011","url":null,"abstract":"<p><p>The emergence of deep learning models such as AlphaFold2 has revolutionized the structure prediction of proteins. Nevertheless, much remains unexplored, especially on how we utilize structure models to predict biological properties. Herein, we present a method using features extracted from protein language models (PLMs) to predict the major histocompatibility complex class II (MHC-II) binding affinity of peptides. Specifically, we evaluated a novel transfer learning approach where the backbone of our model was interchanged with architectures designed for image classification tasks. Features extracted from several PLMs (ESM1b, ProtXLNet or ProtT5-XL-UniRef) were passed into image models (EfficientNet v2b0, EfficientNet v2m or ViT-16). The optimal pairing of the PLM and image classifier resulted in the final model TransMHCII, outperforming NetMHCIIpan 3.2 and NetMHCIIpan 4.0-BA on the receiver operating characteristic area under the curve, balanced accuracy and Jaccard scores. The architecture innovation may facilitate the development of other deep learning models for biological problems.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9701512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of HZ0412a, a novel potent humanized anti-IL-6 receptor antibody that blocks IL-6R binding to gp130.","authors":"Jianzhong Han,&nbsp;Xiaolei Liu,&nbsp;Yue Xu,&nbsp;Qian Wang,&nbsp;Li Li,&nbsp;Kehe Du,&nbsp;Chenchen Li,&nbsp;Hongjun Liu,&nbsp;Yu Chen,&nbsp;Jian Huang","doi":"10.1093/abt/tbad008","DOIUrl":"https://doi.org/10.1093/abt/tbad008","url":null,"abstract":"<p><p>Dysregulated elevation of interleukin-6 (IL-6) signaling is implicated in the pathogenesis of multiple pathophysiological states, and the functional neutralization of the IL-6 pathway with monoclonal antibodies has been proven an effective therapeutic method in treating various diseases with abnormally enhanced IL-6 signaling, and its clinical indications are expanding. Here, we report that by using the conventional hybridoma technology and humanization mutation method, we develop a novel humanized anti-IL-6 receptor (IL-6R) antibody-namely, HZ0412a. In our study, we found that HZ0412a exhibits higher binding affinity to soluble recombinant human IL-6R than tocilizumab. Importantly, in contrast to tocilizumab-a humanized anti-IL-6R antibody approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis and Castleman's disease-HZ0412a does not significantly affect the binding of IL-6 to IL-6R. Further analysis revealed that HZ0412a prevents IL-6R from binding to gp130 <i>in vitro</i>, while tocilizumab has a minimal effect under the same condition. Using various cell-based assays, we demonstrate that HZ0412a is noninferior to tocilizumab in inhibiting IL-6 signaling. Finally, we showed that HZ0412a is well tolerated in cynomolgus monkeys after a single subcutaneous injection at a dose of 1 or 5 mg/kg. Taken together, our results indicated that HZ0412a targets an epitope on human IL-6R that is different from that of tocilizumab, and the epitope region is essential for the interaction between IL-6R and gp130. This distinctive mode of action plus its high affinity to IL-6R led to the high potency of HZ0412a in suppressing <i>in vitro</i> IL-6 signaling.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/23/tbad008.PMC10262838.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9656025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thanks to Our Reviewers in 2022.","authors":"","doi":"10.1093/abt/tbad005","DOIUrl":"https://doi.org/10.1093/abt/tbad005","url":null,"abstract":"","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9319805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status of drug development for patients with multiple myeloma: a review of comparison in China and the rest of world.","authors":"Lei Huang,&nbsp;Jingyu Zhang,&nbsp;Elizabeth Punnoose,&nbsp;Zhenyu Xiao,&nbsp;Wenjin Li","doi":"10.1093/abt/tbad010","DOIUrl":"https://doi.org/10.1093/abt/tbad010","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a highly heterogeneous malignancy. The treatment of MM has been significantly advanced in recent years. B cell maturation antigen (BCMA)-targeted immunotherapy and chimeric antigen receptor T (CAR-T) cell therapy have been approved for the treatment of relapsed and refractory MM (RRMM), which will be launched in China shortly. The CD38 (cluster of differentiation 38) antibody, daratumumab, improves the clinical outcomes both RRMM and newly diagnosed MM patients. The combination of daratumumab, bortezomib and dexamethasone achieved favorable outcomes as the first-line therapy in China. However, high-risk patients have limited benefits from these advanced therapeutics, and usually relapse early, progressing into aggressive end-stage MM. Therefore, novel therapies are sought to improve the cancer prognosis in these patients. This review furnishes an overview of the recent clinical developments of these novel drugs and compares the drug candidates under development in China to the rest of the world.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/88/2a/tbad010.PMC10262841.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9656027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of ISH0339, a tetravalent broadly neutralizing bispecific antibody against SARS-CoV-2 with long-term protection.","authors":"Huabing Yang,&nbsp;Yuxin Chen,&nbsp;Dongcheng Jiang,&nbsp;Xiaoli Feng,&nbsp;Ying Xu,&nbsp;Jiayu Wei,&nbsp;Qingcui Zou,&nbsp;Qiaojiang Yang,&nbsp;Jihong Chen,&nbsp;Xiaoling Jiang,&nbsp;Chunling Qin,&nbsp;Zhenzhen Huang,&nbsp;Chongbing Wu,&nbsp;Ying Zhou,&nbsp;Minghua Li,&nbsp;Liusong Yin","doi":"10.1093/abt/tbad003","DOIUrl":"https://doi.org/10.1093/abt/tbad003","url":null,"abstract":"<p><strong>Background: </strong>Ending the global COVID-19 pandemic requires efficacious therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, the emerging Omicron sublineages largely escaped the neutralization of current authorized monoclonal antibody therapies. Here we report a tetravalent bispecific antibody ISH0339, as a potential candidate for long-term and broad protection against COVID-19.</p><p><strong>Methods: </strong>We report here the making of ISH0339, a novel tetravalent bispecific antibody composed of a pair of non-competing neutralizing antibodies that binds specifically to two different neutralizing epitopes of SARS-CoV-2 receptor-binding domain (RBD) and contains an engineered Fc region for prolonged antibody half-life. We describe the preclinical characterization of ISH0339 and discuss its potential as a novel agent for both prophylactic and therapeutic purposes against SARS-CoV-2 infection.</p><p><strong>Results: </strong>ISH0339 bound to SARS-CoV-2 RBD specifically with high affinity and potently blocked the binding of RBD to the host receptor hACE2. ISH0339 demonstrated greater binding, blocking and neutralizing efficiency than its parental monoclonal antibodies, and retained neutralizing ability to all tested SARS-CoV-2 variants of concern. Single dosing of ISH0339 showed potent neutralizing activity for treatment via intravenous injection and for prophylaxis via nasal spray. Preclinical studies following single dosing of ISH0339 showed favorable pharmacokinetics and well-tolerated toxicology profile.</p><p><strong>Conclusion: </strong>ISH0339 has demonstrated a favorable safety profile and potent anti-SARS-CoV-2 activities against all current variants of concern. Furthermore, prophylactic and therapeutic application of ISH0339 significantly reduced the viral titer in lungs. Investigational New Drug studies to evaluate the safety, tolerability and preliminary efficacy of ISH0339 for both prophylactic and therapeutic purposes against SARS-CoV-2 infection have been filed.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/85/tbad003.PMC10108555.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9384315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of neutralizing antibodies against SARS-CoV-2, using a high-throughput single-B-cell cloning method.","authors":"Yang Dou,&nbsp;Ke Xu,&nbsp;Yong-Qiang Deng,&nbsp;Zijing Jia,&nbsp;Jun Lan,&nbsp;Xiaoyu Xu,&nbsp;Guorui Zhang,&nbsp;Tianshu Cao,&nbsp;Pan Liu,&nbsp;Xiangxi Wang,&nbsp;Xinquan Wang,&nbsp;Lingjie Xu,&nbsp;Pan Du,&nbsp;Cheng-Feng Qin,&nbsp;Hong Liu,&nbsp;Yafeng Li,&nbsp;Guizhen Wu,&nbsp;Kang Wang,&nbsp;Bai Lu","doi":"10.1093/abt/tbad002","DOIUrl":"https://doi.org/10.1093/abt/tbad002","url":null,"abstract":"<p><strong>Background: </strong>Rapid and efficient strategies are needed to discover neutralizing antibodies (nAbs) from B cells derived from virus-infected patients.</p><p><strong>Methods: </strong>Here, we report a high-throughput single-B-cell cloning method for high-throughput isolation of nAbs targeting diverse epitopes on the SARS-CoV-2-RBD (receptor binding domain) from convalescent COVID-19 patients. This method is simple, fast and highly efficient in generating SARS-CoV-2-neutralizing antibodies from COVID-19 patients' B cells.</p><p><strong>Results: </strong>Using this method, we have developed multiple nAbs against distinct SARS-CoV-2-RBD epitopes. CryoEM and crystallography revealed precisely how they bind RBD. In live virus assay, these nAbs are effective in blocking viral entry to the host cells.</p><p><strong>Conclusion: </strong>This simple and efficient method may be useful in developing human therapeutic antibodies for other diseases and next pandemic.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/be/tbad002.PMC10108556.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9752879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond antibody fucosylation: α-(1,6)-fucosyltransferase (Fut8) as a potential new therapeutic target for cancer immunotherapy.","authors":"Changchuin Mao,&nbsp;Jun Li,&nbsp;Lili Feng,&nbsp;Wenda Gao","doi":"10.1093/abt/tbad004","DOIUrl":"https://doi.org/10.1093/abt/tbad004","url":null,"abstract":"<p><p>Aberrant post-translational glycosylation is a well-established hallmark of cancer. Altered core fucosylation mediated by α-(1,6)-fucosyltransferase (Fut8) is one of the key changes in tumor glycan patterns that contributes to neoplastic transformation, tumor metastasis, and immune evasion. Increased Fut8 expression and activity are associated with many types of human cancers, including lung, breast, melanoma, liver, colorectal, ovarian, prostate, thyroid, and pancreatic cancer. In animal models, inhibition of Fut8 activity by gene knockout, RNA interference, and small analogue inhibitors led to reduced tumor growth/metastasis, downregulation of immune checkpoint molecules PD-1, PD-L1/2, and B7-H3, and reversal of the suppressive state of tumor microenvironment. Although the biologics field has long benefited tremendously from using <i>FUT8</i> ^-/- Chinese hamster ovary cells to manufacture IgGs with greatly enhanced effector function of antibody-dependent cellular cytotoxicity for therapy, it is only in recent years that the roles of Fut8 itself in cancer biology have been studied. Here, we summarize the pro-oncogenic mechanisms involved in cancer development that are regulated by Fut8-mediated core fucosylation, and call for more research in this area where modifying the activity of this sole enzyme responsible for core fucosylation could potentially bring rewarding surprises in fighting cancer, infections, and other immune-related diseases.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/4c/tbad004.PMC10108557.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10290416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}