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Use of Immunotherapy in Gynaecological and Breast Cancer
Published in Shazia Rashid, Ankur Saxena, Sabia Rashid, Latest Advances in Diagnosis and Treatment of Women-Associated Cancers, 2022
Showket Hussain, Sandeep Sisodiya, Vishakha Kasherwal, Sonam Tulsyan, Asiya Khan
Bispecific antibodies have two arms: one binds with tumour-associated antigen and another with the activator receptor on effector cells, which activates the cytolytic activity for killing the tumour cell [32–33]. In 2009, the first bsAb, named catumaxomab (trifunctional antibody), was approved and targets epithelial cell adhesion molecules in tumours. Blinatumomab was the second approved bsAb and got an official license in 2014 [34]. These antibody-based therapeutics have recently got attention in treating TNBC patients who are highly metastatic and have poor prognosis [35].
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The most widely studied BsMAbs in the area of cancer therapeutics are engineered to bind simultaneously to a tumor cell and also a naturally occurring cytotoxic cell of the immune system (e.g., a T-lymphocyte) via a receptor such as CD3 (Figure 7.49B). Thus, bispecific antibodies have a significant advantage over ordinary monoclonal antibodies which do not activate T-lymphocytes because (unlike macrophages, NK cells, or dendritic cells) this type of cell does not possess Fc receptors that the Fc region of the antibody can bind to. Another potential advantage is that bispecific antibodies appear to bind to weakly expressed antigens at an effective dose several orders of magnitude lower than for ordinary antibodies.
Role of Engineered Proteins as Therapeutic Formulations
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Khushboo Gulati, Krishna Mohan Poluri
Another strategy that is being employed for the construction of antibody-based drugs includes bispecific antibodies, which unites the specificities of two antibodies and hence can simultaneously respond to different antigens. Catumaxomab (Removab®, anti-EpCAM x anti-CD3) was the first bispecific antibody. It was approved in Europe (2009) to cure malignant ascites in patients with EpCAM-positive carcinomas (Linke et al., 2010). Bispecific antibodies provides an advantage of targeting the two mediators of the disease simultaneously; hence, they are more effective therapeutic agents as compared to those that target the single disease mediator (Marvin and Zhu, 2005).
Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity
Published in mAbs, 2023
Xinghua Pang, Zhaoliang Huang, Tingting Zhong, Peng Zhang, Zhongmin Maxwell Wang, Michelle Xia, Baiyong Li
The development of immuno-oncology (IO) therapies have made substantial progress in recent years, and monoclonal antibodies (mAbs) that target the immune checkpoint programmed cell death-1 (PD-1) have been accepted as the standard of care in a number of tumor types. Numerous combination therapies with anti-PD-1 antibody to improve the efficacy of PD-1 monotherapy have been widely investigated. Current clinical studies have shown that combination therapy of anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) and anti-PD-1 antibodies could produce significantly improved efficacy for some hard-to-treat cancer types, such as renal cell cancer, gastric cancer, and small cell lung cancer, but the application has been limited by severe toxicities.1–5 Therefore, new approaches to achieve the efficacy benefit of PD-1 and CTLA-4 antibodies combination while lowering toxicities present a promising direction of IO drug research. Use of bispecific antibodies is one of the approaches being explored.
Combinatorial therapeutic strategies for enhanced delivery of therapeutics to brain cancer cells through nanocarriers: current trends and future perspectives
Published in Drug Delivery, 2022
Xiande Wang, Cheng Wu, Shiming Liu, Deqing Peng
Dual-targeting strategies can be divided into two main types including (i) that work directly on target structures i.e., soluble factors or cell surface receptors and (ii) that use dual-targeting for delivery of a therapeutically active drug, e.g., effector cells and effector molecules (Kontermann, 2012). Direct actions include neutralization and binding of two receptors or two ligands, neutralization of a ligand and a receptor, activation of two receptors, activation of one receptor and neutralization of another receptor or a soluble factor. It may also include neutralization by binding to different epitopes of one receptor or ligand. Indirect actions include antibody-dependent cell-mediated cytotoxicity (ADCC) and cell dependent cytotoxicity (CDC) through Fc region, targeting of an effector molecule, e.g., a cytokine or a toxin, or a prodrug-converting enzyme, retargeting of immune effector cells through a remote binding site, and targeting of drugs loaded nanocarriers. In certain cases, the indirect and direct actions are combined in one system to further enhance its efficacy (Kontermann, 2012). Dual-targeting techniques have a wide range of applications, especially in cancer therapy. Bispecific antibodies can target the same pathways that are exploited in antibody combination treatment. The dual-targeting antibody can thus target and block many disease mediators and signaling pathways at the same time (Chan & Carter, 2010). This comprises targets that act independently on distinct paths, as well as targets that can cross-talk with one another.
Antibody therapeutics for epithelial ovarian cancer
Published in Expert Opinion on Biological Therapy, 2022
Mason Ruiz, Ningyan Zhang, Anil K Sood, Zhiqiang An
Bispecific antibodies contain two arms that can bind to two different antigens, either different proteins or different epitopes on the same protein. When compared to monoclonal antibodies, bispecific constructs may be advantageous due to increased efficacy, broader coverage of tumor types, reduced off-target toxicity, and reduced drug resistance, although these factors should be carefully considered on a case-by-case basis. One example of bispecific antibodies are bispecific T-cell engagers (BiTEs), which functions as bridges to connect immune effector cells to a target antigen, such as ABBV-428 which connects a T cell CD3 receptor to an overexpressed protein on the surface (e.g. MUC16 in HGSCs) [74]. This immune cell redirection may help to overcome the poor clinical response rate traditionally seen with immune checkpoint monotherapy in ovarian cancer.