Article
Medicine, Research & Experimental
Lian-sheng Cheng, Yong-feng Cheng, Wen-ting Liu, Aolin Shen, Dayan Zhang, Tingjuan Xu, Wu Yin, Min Cheng, Xiaopeng Ma, Fengrong Wang, Qun Zhao, Xiaoli Zeng, Yan Zhang, Guodong Shen
Summary: The study introduced a humanized anti-4-1BB IgG4 antibody, HuB6, targeting a unique epitope and promoting antitumor immunity with high safety. HuB6 demonstrated specificity and affinity for its binding epitope, induced stimulation of CD8 + T, CD4 + T, and NK cells, and inhibited CRC tumor growth in a dose-dependent manner. Additionally, combination of HuB6 with an anti-PD-L1 antibody showed significant inhibition of CRC growth in vivo, indicating its potential as a candidate for further clinical development in CRC immunotherapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Po-Lin Huang, Hung-Tsai Kan, Ching-Hsuan Hsu, Hsin-Ta Hsieh, Wan-Chien Cheng, Ren-Yeong Huang, Jhong-Jhe You
Summary: The bispecific antibody AP203, targeting PD-L1 and CD137, demonstrates potent antitumor activity by blocking inhibitory signaling and activating costimulatory signaling in effector T cells. This leads to enhanced T cell activation, memory recall responses, and a reduction in Treg-mediated immunosuppression. The preclinical results suggest that AP203 is a promising candidate for clinical treatment of solid tumors.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Nora Berois, Alvaro Pittini, Eduardo Osinaga
Summary: Aberrant glycosylation is a common feature of cancer and can lead to changes that affect tumor behavior. Glycans can serve as a source of new clinical biomarkers, providing specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy.
Article
Cell Biology
Amarendra Pegu, Ling Xu, Megan E. DeMouth, Giulia Fabozzi, Kylie March, Cassandra G. Almasri, Michelle D. Cully, Keyun Wang, Eun Sung Yang, Joana Dias, Christine M. Fennessey, Jason Hataye, Ronnie R. Wei, Ercole Rao, Joseph P. Casazza, Wanwisa Promsote, Mangaiarkarasi Asokan, Krisha McKee, Stephen D. Schmidt, Xuejun Chen, Cuiping Liu, Wei Shi, Hui Geng, Kathryn E. Foulds, Shing-Fen Kao, Amy Noe, Hui Li, George M. Shaw, Tongqing Zhou, Constantinos Petrovas, John-Paul Todd, Brandon F. Keele, Jeffrey D. Lifson, Nicole A. Doria-Rose, Richard A. Koup, Zhi-Yong Yang, Gary J. Nabel, John R. Mascola
Summary: The use of trispecific bNAbs can effectively reduce viremia and maintain low levels of virus in the body through immune control. Compared to single bNAbs, trispecific bNAbs can suppress the emergence of resistance and minimize the potential for immune escape.
Review
Biochemistry & Molecular Biology
Lidong Wang, Yang Wang, Hao Zhou
Summary: The development of neutralizing antibodies is crucial for addressing the Omicron variant, but most antibodies have lost their ability to neutralize Omicron. Only a few antibodies remain effective in neutralizing most Omicron subvariants.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Huixin Liang, Wei Wang, Fugui Zhu, Shuqiang Chen, Dan Liu, Chunquan Sheng
Summary: A series of novel bis-evodiamine derivatives inspired by the antitumor natural product evodiamine were synthesized, and they exhibited potent antitumor activity. Notably, compound 13b effectively inhibited the proliferation and migration of HCT116 cells. Mechanistic studies further revealed that compound 13b induced apoptosis in HCT116 cells and arrested the cell cycle at the G2/M phase. Therefore, compound 13b represents a promising lead compound for the discovery of novel antitumor agents.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Hye-Young Min, Yijae Lim, Hyukjin Kwon, Hye-Jin Boo, Seung Yeob Hyun, Junhwa Hong, Suckchang Hong, Ho-Young Lee
Summary: The evodiamine derivative, EV408, has shown potent inhibitory effects on non-small cell lung cancer (NSCLC) cells by inducing apoptosis, suppressing colony formation and CSC population, and destabilizing HSP70 function. It also exhibited negligible toxicity on normal cells.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Gang Li, Jia-Qiang Wu, Xiaojia Cai, Wen Guan, Zhijun Zeng, Yanghui Ou, Xiaoyun Wu, Jiayu Li, Xiangxiang Fang, Jinling Liu, Yali Zhang, Huamin Wang, Canqiang Yin, Hongliang Yao
Summary: A series of diaryl heterocyclic analogues were synthesized as tubulin polymerization inhibitors. Compound 6y exhibited the highest antiproliferative activity against HCT-116 colon cancer cells and effectively inhibited tubulin polymerization in vitro. It also showed high metabolic stability on human liver microsomes and suppressed tumor growth in a HCT-116 mouse colon model without toxicity. These results suggest that 6y represents a new class of tubulin inhibitors worthy of further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yoshiyuki Manabe, Yuki Iizuka, Ryuku Yamamoto, Keita Ito, Kanae Hatano, Kazuya Kabayama, Koichi Fukase
Summary: In this study, the researchers demonstrated that antibody dynamics on membranes can be modulated through glycan conjugation, leading to enhanced antibody activity. This new approach has the potential to improve antibody drugs that lack sufficient activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Analytical
Gang Wu, Chuanfei Yu, Wenbo Wang, Jialiang Du, Zhihao Fu, Gangling Xu, Meng Li, Lan Wang
Summary: Imaged capillary isoelectric focusing (icIEF) and ion exchange chromatography (IEX) are routinely used for charge variant analysis of therapeutic monoclonal antibodies (mAbs). In this study, icIEF-MS and strong cation exchange (SCX)-MS were compared, and it was found that icIEF-MS outperformed SCX-MS in terms of sensitivity, carryover effect, protein identification, and separation resolution.
ANALYTICAL CHEMISTRY
(2023)
Article
Cell Biology
Jenna J. Guthmiller, Julianna Han, Lei Li, Alec W. Freyn, Sean T. H. Liu, Olivia Stovicek, Christopher T. Stamper, Haley L. Dugan, Micah E. Tepora, Henry A. Utset, Dalia J. Bitar, Natalie J. Hamel, Siriruk Changrob, Nai-Ying Zheng, Min Huang, Florian Krammer, Raffael Nachbagauer, Peter Palese, Andrew B. Ward, Patrick C. Wilson
Summary: Broadly neutralizing antibodies targeting conserved receptor-binding site (RBS) or lateral patch epitopes of hemagglutinin (HA) are recalled by first exposure to the 2009 pandemic H1N1 influenza virus. Monoclonal antibodies (mAbs) generated against these epitopes exhibit broad neutralizing activity against H1N1 viruses spanning 40 years of viral evolution, providing potent protection in vivo. Antibodies targeting the lateral patch are found to have near universal binding to H1 viruses, while RBS-binding antibodies commonly cross-react with H3N2 viruses and influenza B viruses.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Jian Xu, Zhihui Shao, Zhanqing Wang, Yingfeng Huang, Xun Zou, Yaling Shen
Summary: This study developed a Her2-binding antibody as a biosimilar to Herceptin, demonstrated glycan profile similarity with cluster analysis, optimized glycosylation using the DoE method, identified significant factors affecting glycosylation pattern, and developed a combination of medium and feed strategy.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Cho Eun Kang, Seungeun Lee, Taeyoung Ahn, Dong Hye Seo, Byoung Joon Ko, Minkyu Jung, Jinu Lee, Joo Young Kim, Woo Taek Kim
Summary: Cancer therapy using immune checkpoint inhibitor antibodies has revolutionized cancer treatment. However, finding a way to eliminate these antibodies' effector function is crucial. In this study, researchers used glycoengineering to remove the cytotoxic effects of antibodies, while preserving their other functions.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Bo Fang, Xue Chen, Xingui Zhou, Xindan Hu, Yan Luo, Zhigang Xu, Cheng-He Zhou, Jiang-Ping Meng, Zhong-Zhu Chen, Chunsheng Hu
Summary: This study presents platinum(IV) compounds with multiple-bond ligands, which exhibited superior activity against tumor cells, proliferation, and metastasis compared to cisplatin. Compounds 2 and 5 with meta-substituted groups showed excellent performance. Research further demonstrated that compounds 2 and 5 had appropriate reduction potential and outperformed cisplatin in cellular uptake, reactive oxygen species response, apoptosis regulation, DNA damage-related gene up-regulation, and drug-resistant cell activity. The title compounds displayed better antitumor potential and fewer side effects in vivo compared to cisplatin. Introduction of multiple-bond ligands improved absorption, overcame drug resistance, and exhibited potential for mitochondrial targeting and inhibition of tumor cell detoxification.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Samantha M. Perez, Julien Dimastromatteo, Charles N. Landen, Kimberly A. Kelly
Summary: The novel CSP-targeting monoclonal antibody 1H11 demonstrated potent anticancer activity against ovarian cancer by inducing significant and selective cytotoxicity, cell cycle arrest, and inhibiting cell migration. In vivo studies showed tumor growth inhibition, tumor necrosis, and increased sensitivity to chemotherapy.
Article
Oncology
Ardalan Mahmoodi, Ahmed Shoqafi, Ping Sun, Vasily Giannakeas, Cezary Cybulski, Sharon Nofech-Mozes, Jean-Yves Masson, Sudha Sharma, Amir Abbas Samani, Srinivasan Madhusudan, Steven A. Narod, Mohammad R. Akbari
Summary: The study found that high RECQL protein levels are associated with improved survival rates in breast cancer patients who are ER-positive, but no significant association was found in ER- patients. Additionally, in ER-negative patients receiving tamoxifen treatment, high RECQL protein levels may be associated with better survival rates.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Reem Ali, Mustapha Aouida, Abdallah Alhaj Sulaiman, Srinivasan Madhusudan, Dindial Ramotar
Summary: Cisplatin is one of the oldest chemotherapeutic agents and has been used to treat various types of cancer. However, tumor cells often develop resistance mechanisms, limiting the effectiveness of cisplatin treatment. Extensive molecular and genetic profiling of patients is needed to identify individuals who can benefit from cisplatin therapy, and combining it with targeted therapies may improve treatment outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Kazuyo Kaneko, Abed M. Zaitoun, Darren P. Letley, Joanne L. Rhead, Javier Torres, Ian Spendlove, John C. Atherton, Karen Robinson
Summary: The study found that CD55 expression levels significantly increased in Helicobacter pylori-infected patients and were associated with intestinal metaplasia (IM), but not with gastric atrophy or inflammation. Infection with vacA i1-type strains was linked to increased gastric CD55 expression and IM.
JOURNAL OF PATHOLOGY
(2022)
Article
Oncology
Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Summary: Platinum resistance is a major challenge in ovarian cancer treatment. This study comprehensively evaluated the expression and function of Mre11 in epithelial ovarian cancers, and found that overexpression of Mre11 was associated with aggressive phenotype and poor progression free survival. In addition, Mre11 gene amplification was observed in a subset of serous tumors and correlated with Mre11 mRNA levels. Furthermore, Mre11 overexpression at the transcriptomic level was linked with poor survival. Preclinical experiments showed that depletion or blockade of Mre11 reversed platinum resistance in ovarian cancer cells, and selective cytotoxicity was observed in platinum-sensitive XRCC1 deficient cells. These findings suggest that pharmaceutical development of Mre11 inhibitors could be a promising clinical strategy for sensitizing ovarian cancer to platinum and inducing synthetic lethality.
NPJ PRECISION ONCOLOGY
(2022)
Article
Oncology
Daisy B. Haigh, Corinne L. Woodcock, Jennifer Lothion-Roy, Anna E. Harris, Veronika M. Metzler, Jenny L. Persson, Brian D. Robinson, Francesca Khani, Mansour Alsaleem, Atara Ntekim, Srinivasan Madhusudan, Melissa B. Davis, Kristian B. Laursen, Lorraine J. Gudas, Catrin S. Rutland, Michael S. Toss, Nathan Archer, Zsuzsanna Bodi, Emad A. Rakha, Rupert G. Fray, Jennie N. Jeyapalan, Nigel P. Mongan
Summary: This study investigated whether therapies targeting the epitranscriptome can suppress androgen signalling in prostate cancer. The results showed that METTL3 is aberrantly expressed in prostate cancer patients and that knockdown or inhibition of METTL3 can significantly alter the basal and androgen-regulated transcriptome in prostate cancer, suggesting that targeting m6A could be a novel approach to modulate androgen signalling in prostate cancer.
Article
Multidisciplinary Sciences
Jia Xin Chua, Lindy Gillian Durrant, Yin Ling Chok, Oi Ming Lai
Summary: This study compares the efficacy of different COVID-19 vaccines against SARS-CoV-2 variants. The ChAdOx1 nCoV-19 and BNT162b2 vaccines show higher blocking activity against the Spike protein receptor binding domain (RBD) of the wild type virus compared to the CoronaVac vaccine in uninfected individuals. Prior infection enhances the protection provided by the CoronaVac vaccine. Furthermore, all vaccine platforms cross-protect against most variants of concerns except the Omicron variant. Broad sterilizing immunity induced by vaccines is crucial in combating fast-emerging variants.
Article
Oncology
Amit Bahl, William Wilson, Jessica Ball, Emily Renninson, Sidharth Dubey, Alicia Bravo, Emily Foulstone, Saiqa Spensley, Rebecca Bowen, Janine Mansi, Simon Waters, Pippa Riddle, Duncan Wheatley, Peter Stephens, Pavel Bezecny, Srinivasan Madhusudan, Mark Verrill, Jeremy Braybrooke, Charles Comins, Vivek Mohan, Abigail Gee, Hannah Kirk, Alison Markham, Heidi Evans, Eve Watson, Mark Callaway, Sylvia Pearson, Allan Hackshaw, Mark Churn
Summary: In HER2-negative MBC patients, three-weekly cabazitaxel does not significantly improve progression-free survival compared to weekly paclitaxel, but it has a lower risk of peripheral neuropathy and better quality of life outcomes.
Article
Cell Biology
Ayat Lashen, Michael S. Toss, Wakkas Fadhil, Georgette Oni, Srinivasan Madhusudan, Emad Rakha
Summary: This study aimed to compare the performance of Oncotype DX with conventional clinicopathological parameters in ER+/HER2- breast cancer. The results showed a significant correlation between Oncotype DX and tumor grade, type, ER and PR expression, and Ki67 index. Therefore, these tumor features can be used as surrogate markers in certain scenarios.
Article
Medicine, General & Internal
Sara A. Hurvitz, Roberto Hegg, Wei-Pang Chung, Seock-Ah Im, William Jacot, Vinod Ganju, Joanne Wing Yan Chiu, Binghe Xu, Erika Hamilton, Srinivasan Madhusudan, Hiroji Iwata, Sevilay Altintas, Jan-Willem Henning, Giuseppe Curigliano, Jose Manuel Perez-Garcia, Sung-Bae Kim, Vanessa Petry, Chiun-Sheng Huang, Wei Li, Jean-Sebastien Frenel, Silvia Antolin, Winnie Yeo, Giampaolo Bianchini, Sherene Loi, Junji Tsurutani, Anton Egorov, Yali Liu, Jillian Cathcart, Shahid Ashfaque, Javier Cortes
Summary: In the DESTINY-Breast03 trial, trastuzumab deruxtecan showed superior progression-free survival compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer. The study aimed to compare the efficacy and safety of trastuzumab deruxtecan versus trastuzumab emtansine. The results demonstrated that trastuzumab deruxtecan had the longest reported median progression-free survival and improved overall survival, reaffirming its role as the standard of care in the second-line setting.
Article
Genetics & Heredity
Ruben D. D. Houvast, Maurice van Duijvenvoorde, JiaXin Chua, Mireille Vankemmelbeke, Lindy G. G. Durrant, Akin Inderson, Jeanin E. E. van Hooft, J. Sven D. Mieog, Bert A. A. Bonsing, Cornelis F. M. Sier, A. Stijn L. P. Crobach, Alexander L. L. Vahrmeijer, Peter J. K. Kuppen
Summary: This study evaluated whether fine-needle biopsy (FNB) specimens could be used to predict biomarker expression in the corresponding primary PDAC specimen. The results showed high concordance between biomarker expression in FNB and primary tumor tissues, providing the foundation for the clinical application of an FNB-based biomarker-screening workflow.
MOLECULAR DIAGNOSIS & THERAPY
(2023)
Article
Immunology
Victoria Anne Brentville, Peter Symonds, JiaXin Chua, Anne Skinner, Ian Daniels, Katherine Wendy Cook, Sasa Koncarevic, Roxana Martinez-Pinna, Sabaria Shah, Ruhul Hasan Choudhury, Poonam Vaghela, Daisy Weston, Abdullah Al-Omari, James Davis, Lindy G. Durrant
Summary: Post translational modification of proteins, such as citrullination, plays a significant role in immune recognition. Targeting citrullinated GRP78 shows potential for cancer therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Mashael Algethami, Sanat Kulkarni, Maaz T. Sadiq, Hiu K. C. Tang, Juliette Brownlie, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Summary: Despite the poor overall outcomes for patients with advanced ovarian cancer, a precision medicine strategy focusing on DNA repair, such as PARP inhibitors, has shown promising results in improving survival. Additionally, antiangiogenic agents, intraperitoneal chemotherapy, and immunotherapeutic approaches could also positively impact patient outcomes.
CANCER MANAGEMENT AND RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Juliette Brownlie, Sanat Kulkarni, Mashael Algethami, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Summary: DNA repair targeted therapeutics, such as PARP inhibitors, have shown promising results in the treatment of BRCA germline deficient breast and ovarian cancer. However, not all patients respond to this treatment due to intrinsic or acquired resistance. Therefore, the exploration of other synthetic lethality approaches, including ATM, ATR, and WEE1 inhibitors, is currently an active area in cancer research.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Hiu Tang, Sanat Kulkarni, Christina Peters, Jasper Eddison, Maryam Al-Ani, Srinivasan Madhusudan
Summary: Despite advances in chemotherapy and surgery, patients with advanced ovarian cancer still have poor survival outcomes. Platinum-based systemic chemotherapy can lead to a high response rate, but most patients will experience recurrence and succumb to the disease. The use of PARP inhibitors in BRCA germ-line-deficient and/or platinum-sensitive epithelial ovarian cancers has improved survival, but resistance remains a clinical challenge. This review discusses the current clinical state of PARP inhibitors and other targeted approaches in epithelial ovarian cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Hiu Tang, Daniel Yeo, Karen De Souza, Omar Ahmad, Tahir Shafiq, Okezie Ofor, Anjana Anand, Syed Karim, Sarah Khan, Srinivasan Madhusudan
Summary: CDK4/6 inhibitors can significantly increase progression-free survival in ER+/HER2- advanced breast cancer patients. There is no significant difference in PFS and OS between different drugs in real-world evaluation. De novo disease and PR+ disease have longer PFS and OS. Very elderly patients have shorter PFS and OS.
