Bispecific antibodies are antibodies that can simultaneously recognize two different antigens or epitopes. They have multiple structures and functions and can be used to treat various diseases, especially tumors. The development of bispecific antibodies has gone through several stages, from the initial chemical ligation method to the later genetic engineering method, which has continuously improved their stability, affinity, and efficiency. At present, a variety of bispecific antibodies have entered clinical trials or been approved for marketing, showing good safety and efficacy.
The rationale for bispecific antibody recruitment of immune cells through cell bridging is that one arm of the bispecific antibody can specifically recognize an antigen on tumor cells, and the other arm can specifically recognize an activating receptor on immune cells. This forms a bridge between tumor cells and immune cells, promoting the activation, proliferation, and killing functions of immune cells and leading to the elimination of tumor cells. According to the type of immune cells, the recruitment of immune cells by bispecific antibodies through cell bridging can be divided into two types: T cell bridging and NK cell bridging. T cell bridging means that one arm of the bispecific antibody can recognize antigens such as CD19, CD20, and CD22 on tumor cells, and the other arm can recognize activating receptors such as CD3 and CD28 on T cells. This recruits T cells to fight against tumor cell killing. NK cell bridging means that one arm of the bispecific antibody can recognize antigens such as HER2, EGFR, and CEA on tumor cells, and the other arm can recognize activating receptors such as CD16 and NKG2D on NK cells. This recruits NK cells to fight against tumor cell killing. These two types of bispecific antibodies have their own structural characteristics, mechanisms of action, representative drugs, and clinical effects.
The main feature of bispecific antibodies recruiting immune cells through cell bridging is that they can efficiently link immune cells and tumor cells together, thereby enhancing the killing ability of immune cells and reducing the damage caused by immune cells to normal tissues. Bispecific antibodies have high specificity, which means they can only recognize specific antigens or epitopes. This allows them to avoid non-specific binding and activation, improving the safety and effectiveness of treatment. Bispecific antibodies also have low toxicity, meaning they do not cause serious side effects such as cytokine storm, hematological toxicity, or neurotoxicity - which are common with other types of immunotherapies. Additionally, bispecific antibodies do not cause drug resistance in tumor cells, as they do not directly act on tumor cells but instead kill them through immune cells that can adapt to changes in tumor cells. Compared to other types of bispecific antibodies or monoclonal antibodies, bispecific antibodies have obvious advantages in recruiting immune cells through cell bridging. However, they also have some disadvantages, such as poor stability, short half-life, and high production costs, which need to be addressed in future research.
The scope of application of immune cell recruiting with bispecific antibodies is mainly for tumors with clear tumor-specific antigens and immune cell activation receptors, such as hematological tumors, breast cancer, and colorectal cancer. It is important for the target combination of bispecific antibodies to have high affinity, high selectivity, and high expression to ensure effective bridging between tumor cells and immune cells. The patients who can benefit from bispecific antibodies should have good immune function and tolerance to produce a durable immune response and avoid serious adverse reactions. This includes patients with normal or low immune function, patients who have failed chemotherapy or radiotherapy, and patients with multidrug resistance. The scope of application continues to expand with the discovery of new tumor-specific antigens and immune cell activation receptors, as well as the design and optimization of new bispecific antibodies. It is expected that a wide variety of tumor types, target combinations, and patient populations will benefit from this innovative immunotherapy.
In conclusion, the use of bispecific antibodies to recruit immune cells through cell bridging is an innovative immunotherapy strategy that efficiently connects immune cells and tumor cells. This strategy enhances the killing ability of immune cells while minimizing damage to normal tissues.
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