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Recent Advances of Nanotechnologies for Cancer Immunotherapy Treatment
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
mAb belonging to the IgG class has been widely studied for cancer immunotherapy [378]. mAb mediates tumor cell depletion by binding to a specific surface antigen at the cancer cells, triggering antigen-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are both dependent on the host immune system. mAb targeting the immune checkpoint has been developed to improve the antitumor immune response [379]. For example, Ipilimumab (Yervoy®) and Tremelimumab (CP-675,206) bind to CTLA-4 receptor in T cells and block the inhibitory function against the costimulatory receptor CD28, thereby enhancing the T cell-DC interaction and reducing the number of Treg [165,180,380]. Nivolumab (Opdivo®), Pidilizumab (C-011), and Pembrolizumab (Keytruda®) target the programmed death signal-1(PD-1) receptor, another negative regulator on the T-cell surface that reduces the interaction with TAAs. Blocking the PD-1 receptor results in enhanced activation of T cells and decreased Treg infiltration to the tumor [381]. Among other immune mAbs, Daclizumab (Zinbryta®), an anti-CD25 mAb [382]; Dacetuzumab, an anti-CD40 mAb [383]; and Durvalumab (Imfinzi®) [384] and Avelumab (Bavencio®) [385], as anti-PD-L1 mAbs, are currently approved or in last stages of clinical trials for cancer immunotherapy.
Aptamers: Scope, Limitations, and Future Prospects
Published in Rakesh N. Veedu, Aptamers, 2017
Nobel laureate Kary Mullis has patented aptamer-alpha-gal sugar conjugates for his company Altermune, LLC, which noncovalently bind to the 1% of anti-alpha-gal (galactose-alpha-1,3-galactose) circulating antibodies in human serum [71, 88] to increase weight and retard organ clearance [39, 43, 58] of the aptamer-alphagal complex. Binding to circulating antibodies also imparts the functionality of the antibody’s Fc tail to activate complement and allow phagocytosis or antibody-dependent cellular cytotoxicity (ADCC) [18, 19, 30, 71, 88]. The only potential deficiency of Altermune’s approach is that the aptamer-alpha-gal conjugate must find and bind its cognate antibody before being eliminated by the kidneys or liver [39, 43, 58, 70]. While some aptamer-alpha-gal-antibody complexes will undoubtedly form, some aptamer-alphagal conjugates will probably also be lost to the kidneys before encountering protective antibodies. It, therefore, makes greater sense to the author to inoculate with premade heavy aptamer-3′-protein covalent conjugates as he has published [25] and patented (US Patent Nos. 7910297, 8318920, and 8389710).
Biomaterial Surface Properties
Published in Nihal Engin Vrana, Biomaterials and Immune Response, 2018
Tuğba Endoğan Tanır, Güneş Esendağlı, Eda Ayşe Aksoy
Once the antigens arrive in the lymph nodes, the B-cells are simultaneously activated with T-cells. B-cells, adaptive immunity cells with antibody production, antigen memory and antigen-presenting roles, can recognise soluble, concentrated antigens in the lymph nodes directly (i.e., without a need for an antigen-presenting cell unlike T-cells). In fact, B-cells internalise the antigen for presentation to T-cells. B-cells recognise antigens by membrane-bound Igs (surface antibodies). After being activated, B-cells also produce antibodies in soluble form for antigen elimination. B-lymphocytes are another critical subset that need help from T-cells to react more specifically and efficiently. Once a Th1-type immune response is initiated, activated B-cells start to produce more IgGs than IgMs, which are more effective and specified in immunity. Some of the B-cells differentiate into plasma cells (which have significant longevity) with a high capacity to produce antibodies. Binding of the secreted antibodies with the antigens with high specificity and affinity results in the triggering of cytotoxic activities towards the invading organisms containing the given antigen. The antibody coating of the target cells or materials can be easily recognised by phagocytes such as NKs and they are subsequently eliminated by a process defined as “antibody-dependent cellular cytotoxicity (ADCC)”. Moreover, antibodies can also trigger other defence mechanisms such as induced apoptosis and complement-mediated cell lysis. In addition to T- and B-lymphocytes, there are other minor subsets of adaptive immune cells with different capacities to discriminate between foreign and self-antigens.
Enhancement of anti-TNFα monoclonal antibody production in CHO cells through the use of UCOE and DHFR elements in vector construction and the optimization of cell culture media
Published in Preparative Biochemistry & Biotechnology, 2021
Chinh Chung Doan, Nguyen Quynh Chi Ho, Thi Thuy Nguyen, Thi Phuong Thao Nguyen, Dang Giap Do, Nghia Son Hoang, Thanh Long Le
To assess antibody quality, mAbTNFα was purified using affinity chromatography and ion-exchange chromatography on the AKTA Purifier system. The primary structural and functional properties of purified mAbTNFα were compared to that of adalimumab. As a result, the purified mAbTNFα and adalimumab had the same molecular weight and primary structure (Figures 8 and 9). The primary therapeutic action mechanism of adalimumab is to bind sTNFα at the Fab region, neutralizing the cytotoxic effects of TNFα by binding with high affinity preventing its binding to TNF-α receptors. Quantification of the interaction between the Fab antigen recognition site of the antibody and the epitope of the antigen is fundamental to the functional and therapeutic comparability of biosimilar materials. Our data showed that the sTNFα-binding and TNFα-neutralizing activities of purified mAbTNFα were similar to those of adalimumab (Figures 10A and 11A). In addition, adalimumab may bind to mTNFα, leading to the blockage of TNFα signaling induced by mTNFα or potentially mediating cellular effects directly by engaging mTNFα. The proposed mechanism of action is ADCC, which is an immune defense mechanism in which an effector cell of the immune system actively lyses a target cell to which an antibody binds. In the present study, the ADCC assay used genetically engineered NK cells as effector cells and measured the killing of target CHO cells overexpressing mTNFα as an endpoint of this pathway activation. Our results demonstrated that purified mAbTNFα and adalimumab had the same mTNFα-binding capacity and in vitro ADCC activity (Figures 10B and 11B). Therefore, all of the obtained data indicated acceptable primary functional and structural properties of mAbTNFα, which were comparable to those of adalimumab. However, further studies with a comprehensive set of state-of-the-art analytical techniques are required to demonstrate the biosimilarity of mAbTNFα in comparison with originator adalimumab.