Review
Chemistry, Multidisciplinary
Adilet Beishenaliev, Yean Leng Loke, Sook Jing Goh, Hui Nee Geo, Malar Mugila, Misni Misran, Lip Yong Chung, Lik Voon Kiew, Steve Roffler, Yin Yin Teo
Summary: Monospecific antibodies have limitations in delivering drugs to tumors with multiple epitopes, while bispecific antibodies provide a promising alternative by simultaneously targeting two distinct antigens or epitopes. This review discusses the roles of bispecific antibodies in enhancing the internalization and intracellular trafficking of drug-conjugated antibodies and facilitating the delivery of drug-encapsulating nanoconstructs.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Immunology
Zicheng Hu, Sivan Cohen, Steven J. Swanson
Summary: This study identified a positive correlation between the clinical ADA rate and the number of introduced mutations in the antibody sequences. The use of rare V alleles in human-origin antibody therapeutics was also found to be associated with higher risk of immunogenicity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tingting Liu, Yajun Sun, Xiaojie Deng, Lili Shi, Wenyi Chen, Wenjing Fang, Junliang Wu, Xiaotian Fan, Xiaoqiang Chen, Jianhua Sun, Gang Qin, Likun Gong, Qiuping Qin
Summary: In this study, a acid-dissociation bridging enzyme-linked immunosorbent assay was developed and validated for the detection of antibodies against GQ1001 in cynomolgus monkey serum. The assay showed high sensitivity and specificity and was not affected by other interfering substances. Moreover, it was successfully applied to a single-dose toxicity study of GQ1001, without significant impact on toxicokinetic outcomes.
Review
Oncology
Yanchen Zhou, Hweixian L. Penny, Mark A. Kroenke, Bianca Bautista, Kelly Hainline, Lynette S. Chea, Jane Parnes, Daniel T. Mytych
Summary: This review discusses the immunogenicity risk assessment of bispecific antibodies (BsAbs) and highlights several risk factors, including novel scaffolds, immunomodulating mechanisms of action, and other product and patient-related factors. The clinical relevance of anti-drug antibodies against BsAbs and advances in tools and strategies for immunogenicity prediction, monitoring, and mitigation are also reviewed. Implementing a drug-specific risk assessment during early development is critical for guiding risk management strategies and improving clinical success.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Engineering, Multidisciplinary
Ji-Min Dai, Xue-Qin Zhang, Jing-Yao Dai, Xiang-Min Yang, Zhi-Nan Chen
Summary: The modification of therapeutic antibodies is booming in research and development to improve efficacy. China, as an active player in the biopharmaceutical field, shows a great demand and potential in this area.
Article
Medicine, Research & Experimental
Maria U. Johansson, Christopher Weinert, Dietrich Alexander Reichardt, Dana Mahler, Dania Diem, Christian Hess, Diana Feusi, Simon Carnal, Julia Tietz, Noreen Giezendanner, Fabio Mario Spiga, David Urech, Stefan Warmuth
Summary: Upon reformatting antibody to single-chain variable fragment format, a previously hidden hydrophobic patch in the variable/constant domain interface becomes accessible for preexisting anti-drug antibody binding. To reduce the reactivity of preexisting antibodies and the exposed hydrophobic patch, mutations were introduced in this region. Through computational methods and experimental characterization, mutation of two threonine residues, Thr101 and Thr146, was found to be critical in eliminating preexisting antibody reactivity, which could have important implications in optimizing early drug development for antibody fragment-based therapeutics.
Article
Cell Biology
Vahab Ziaei, Alireza Ghassempour, Fatemeh Davami, Bahareh Azarian, Mahdi Behdani, Hamed Dabiri, Mahdi Habibi-Anbouhi
Summary: Antibody drug conjugates (ADCs) merge monoclonal antibody specificity with chemotherapy cytotoxicity, but face challenges of insufficient internalization, complex structures, and large size. Camelid single domain antibody fragments (Nanobody) provide solutions with nanoscale size, high solubility, recombinant expression, enhanced tissue penetration, and conjugation advantages.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Immunology
Alessandra Vultaggio, Margherita Perlato, Francesca Nencini, Emanuele Vivarelli, Enrico Maggi, Andrea Matucci
Summary: Biologicals are commonly used for rheumatologic diseases, cancers, and chronic inflammatory conditions, but they may lead to the development of anti-drug antibodies (ADA), limiting their clinical usage due to safety concerns. Strategies such as concomitant immunosuppressive treatment and regular infusion regimens can help reduce the risk of immediate hypersensitivity reactions (HSRs) associated with ADA. Drug desensitization (DD) may be considered for patients needing reintroduction of the biological culprit, especially in cases of IgE-mediated HSRs, potentially inhibiting mast cell degranulation and cytokine production.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Lucia Gandullo-Sanchez, Atanasio Pandiella
Summary: By studying resistant clones derived from HER2+ breast cancer cell line, it was found that resistance to T-DM1 was associated with decreased levels of HER2, but the cells still depended on HER2. Antibody array analysis revealed the expression of EGFR in T-DM1-resistant cells, and targeted therapy against EGFR showed an anti-proliferative effect on these cells.
Review
Oncology
Elizabeth Sakach, Ruth Sacks, Kevin Kalinsky
Summary: Trop-2 is a new target for the treatment of breast cancer, with potential therapeutic benefits for metastatic and resistant patients. Inhibitors of Trop-2 have emerged as important treatment options, and ongoing studies investigate combination therapies and its use in early stage disease.
Article
Immunology
Michael D. Swanson, Shantel Rios, Sarita Mittal, George Soder, Vibha Jawa
Summary: Aggregates of therapeutic proteins have been found to increase immunogenicity risks, with spontaneously occurring aggregates able to induce innate immune responses. The impact of different aggregate samples on immune responses may vary.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Michael A. Partridge, Jihua Chen, Elif Kabuloglu Karayusuf, Thanoja Sirimanne, Colin Stefan, Ching Ha Lai, Meghna Gathani, Lisa DeStefano, Michal Rozanski, Sean McAfee, Manoj Rajadhyaksha, Matthew D. Andisik, Albert Torri, Giane Sumner
Summary: The study found that approximately 20% of baseline patient samples showed a pre-existing antibody response to a human IgG4 monoclonal antibody therapy, which could interfere with the detection of newly emerged antibody responses. Competitive inhibition experiments revealed that the majority of these samples had reactivity to an epitope in the CH3 domain of human IgG4 containing leucine 445. The pre-existing response in baseline patient samples could be mitigated by replacing the capture reagent in the assay, without affecting the detection of specific drug and treatment-emergent antibodies.
Article
Biochemistry & Molecular Biology
Yuka Tanaka, Maho Murata, Che-Hung Shen, Masutaka Furue, Takamichi Ito
Summary: The study found that high expression of NECTIN4 is associated with disease-free survival in melanoma, and in BRAFi-resistant melanoma cells, both NECTIN4 and the PI3K/Akt pathway are upregulated. Inhibiting NECTIN4 can increase the sensitivity of BRAFi-resistant cells to BRAFi, offering a novel treatment strategy for melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dian Xiao, Longlong Luo, Jiaguo Li, Zhihong Wang, Lianqi Liu, Fei Xie, Jiannan Feng, Xinbo Zhou
Summary: The study confirmed for the first time that Atezolizumab is more suitable for designing ADCs compared to Avelumab, with the generated ADC 3 exhibiting potent tumor cell inhibitory activity and immune activation effects. These findings have positive implications for cancer therapy.
BIOORGANIC CHEMISTRY
(2021)
Article
Oncology
Guang Wu, Lan Li, Mengnan Liu, Chunyan Chen, Guangze Wang, Zewei Jiang, Yaqian Qin, Licai He, Hongzhi Li, Jiawei Cao, Haihua Gu
Summary: The generated HzMUC1-ADC demonstrated promising targeted therapy potential for pancreatic cancer, as it inhibited tumor cell growth, induced apoptosis, and significantly reduced xenograft tumor growth in vivo.
CANCER CELL INTERNATIONAL
(2022)
