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Introduction
Published in Laszlo Endrenyi, Paul Jules Declerck, Shein-Chung Chow, Biosimilar Drug Product Development, 2017
Laszlo Endrenyi, Paul Declerck, Shein-Chung Chow
Since all biological products are biologically active molecules derived from living cells and have the potential to evoke an immune response, immunogenicity is probably the most critical safety “uncertainty” for the assessment of biosimilarity of follow-on biologics. The commonly seen possible causes of immunogenicity include, but are not limited to: (1) sequence differences between a therapeutic protein and endogenous proteins, (2) nonhuman sequences or epitopes, (3) structural alterations, (4) storage conditions, (5) purification during the manufacturing process, (6) formulation (e.g., surfactants), (7) route, dose, and frequency of administration, (8) patient status such as concomitant therapy (e.g., immunosuppressants) or genetic background. Thus, the following questions should be asked when assessing biosimilarity between biological products: (1) What is the immunogenic potential of the therapeutic protein? (2) What is the impact of the generating antibodies to the self-protein or to the therapeutic drug? (3) What is the impact of immunogenicity on preclinical toxicity (e.g., pharmacokinetic levels and dose-limiting toxicity)? (4) What is the impact of immunogenicity of the therapeutic protein on safety? (5) What are the risk evaluation and mitigation strategy processes required by regulatory agencies?
Overview and Future Trends of Nanosensors
Published in Vinod Kumar Khanna, Nanosensors, 2021
Research is still in the process of defining the various adsorbents and possible selective adsorption of an analyte. One of the approaches that scientists are currently exploring is modifying the surface properties by biocompatible coatings. How do biocompatible coatings function? These coatings inhibit the binding of non-specific elements and, at the same time, they do not affect the analyte. Different polymers are being used for these applications. These polymers should be biocompatible as well as non-immunogenic. Immunogenicity is the ability of a substance to provoke an immune response in the body.
Current Immune Aspects of Biologics and Nanodrugs: An Overview
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
Immunogenicity could be measured by experimental approaches or predicted via mathematical models and in vitro/in vivo/in silico assays. Therefore, few tools have been developed to access potential immunogenicity of biologics and nanodrugs (Table 1.6). The key methods for preclinical measurement of immunogenicity use in silico, in vitro, and in vivo models to predict CD4+ T cell responses as well as conventional mouse models, immune-tolerant transgenic mice, HLA-immune-tolerant transgenic mice, and nonhuman primate models (Table 1.6).
Construction and evaluation of wild and mutant ofatumumab scFvs against the human CD20 antigen
Published in Preparative Biochemistry & Biotechnology, 2023
Reza Maleki, Azam Rahimpour, Masoumeh Rajabibazl
Using whole IgG antibodies could come with some drawbacks as therapeutic anticancer agents, including low blood clearance and high production costs, respectively due to their large size and the need for expression in mammalian cells.[7] There are many techniques developed to eliminate these constraints. For example, recombinant fragments of the antibody such as minibodies (scFv-CH3), Fabs (fragment antigen-binding), and single chain variable fragments (scFv) may diminish the cost of production, increase penetration and relatively, prevent the immunogenicity.[8] As well as this, the E. Coli expression method for antibody generation provides a number of plus points including high rates of expression, affordable cultivation expenses, swift growth, low risk of contamination with viral DNA, non-glycosylation, and simpler purification.[9]
Cloning, large-scale production and characterization of fusion protein (P-TUFT-ALT-2) of Brugian abundant larval transcript-2 with tuftsin in Pichia pastoris
Published in Preparative Biochemistry and Biotechnology, 2018
Rajkumar Paul, Selvarajan Karthik, Ponnusamy Vimalraj, Sankaranarayanan Meenakshisundaram, Perumal Kaliraj
Tuftsin is a naturally occurring nontoxic tetra-peptide immunopotentiator.[25] It increases the immunogenicity of an antigenic protein by directing it to phagocytic cells leading to a sturdier humoral and cellular immune response. Tuftsin has been used with various antigens such as malaria, leprosy, HIV, etc. in vaccine development.[26–28] Tuftsin along with DEC was found to suppress microfilarial stage of parasite till 90 days post treatment. Of great interest, DEC and tuftsin bearing liposomes were also observed as the most effective against adult parasites.[29] New batracylin conjugate with tuftsin derivative with branched side amino acid chain such as leucine or isoleucine exhibited 10-fold more cytotoxic effect on human tumor cell lines such as lung adenocarcinoma (A549) and myeloblastic leukemia (HL-60).[30]
Updates in immunocompatibility of biomaterials: applications for regenerative medicine
Published in Expert Review of Medical Devices, 2022
Mahdi Rezaei, Farideh Davani, Mohsen Alishahi, Fatemeh Masjedi
Vaccine delivery is one of the recent biomaterials applications that require specific immune modifications. In this respect, immune-regulated nanofibers vaccine delivery systems were produced to act as a vaccine adjuvant. Recently peptide nanofibers have drawn vast attention to use as the vaccine delivery system. It was suggested that supermolecular peptide nanofibers could raise the immune response without causing severe inflammation due to their non-covalent construction [154]. Si et al. developed peptide nanofibers to increase the immunogenicity of the influenza lung vaccine. Their obtained results demonstrated that the special characteristic of peptide resulted in the higher CD8+ T cell responses without measurable inflammation in the lung, leading to a suitable vaccine delivery system [155]. Mora-Solano also obtained the same results as their study confirmed the potential of the peptide-based nanofibers as the vaccine delivery systems [156]. The applications of the peptides with surface charge can be more beneficial as charge density can also affect the immune response. Yang et al. fabricated nanofibrous peptide mats with positive and negative surface charges and demonstrated positive cargo in the peptide nanofibers resulting in less immunogenicity and hence, are more promising for the vaccine delivery systems [157]. The same results also were obtained by Zhang et al., who developed differently charged peptide self-assemble nanofibrous scaffolds. The immune response of the devices was evaluated by in vitro and in vivo investigations, and the results demonstrated the cationic peptide nanofibrous scaffold could trigger the less immune response and thus, act as a suitable device for various vaccine delivery applications [158].