Overview of Triple Body

Background of Triple Body

Antibody drugs represent a class of biologics that employ antibodies or their derivatives as active ingredients to prevent or treat human or animal diseases. In fields like cancer, autoimmune diseases, and infectious diseases, antibody drugs have emerged as top-selling pharmaceuticals, demonstrating promising clinical applications. However, they still face certain challenges and obstacles. As a result, continuous exploration of novel technologies and strategies is essential to enhance the quality and efficiency of antibody drugs. Triple body, a cutting-edge multifunctional antibody platform, is composed of three single-chain variable fragments (scFvs), each with distinct targeting specificity, enabling simultaneous recognition of three different antigens or receptors. Its structural design and expression mode differ from traditional bispecific antibodies (BsAbs) and trispecific antibodies (TsAbs), providing enhanced flexibility and stability. Various methods, such as gene recombination, chemical coupling, and enzyme catalysis, can be employed to generate triple body. While triple body offers several advantages in clinical applications, such as the activation of multiple immune cells, improved tumor-killing effects, and expanded therapeutic potential, it also present some limitations, including potential increases in toxicity, immunogenicity, and production difficulties.

Structural Features and Generation Methods of Triple Body

Triple body is a trivalent antibody composed of three single-chain variable fragments (scFvs), each with a unique targeting specificity, enabling simultaneous recognition of three different antigens or receptors. scFv, the smallest antibody unit composed of heavy and light chain variable regions connected by a peptide linker, ensures high stability and expression efficiency. The three scFvs in triple body can be combined in different arrangements and connection modes, leading to various types of triple bodies, such as tandem, parallel, Y-shaped, T-shaped, among others. The structural design and expression mode of triple body differ significantly from traditional bispecific antibodies (BsAbs) and trispecific antibodies (TsAbs), providing heightened flexibility and stability.

Fig.1 Triple Bodies for the Treatment of Cancer

Triple body can be generated through diverse methods, including gene recombination, chemical coupling, and enzyme catalysis. The gene recombination method involves using molecular biology technology to connect the three scFv genes into a single expression vector, which is then expressed and purified in the desired triple body by transfecting host cells. The chemical coupling method employs specific chemical reactions to introduce functional groups on the three scFv molecules, leading them to undergo cross-linking reactions under appropriate conditions, forming stable covalent bonds, and producing the desired triple body. Lastly, the enzyme catalysis method utilizes enzyme-catalyzed reactions to introduce specific substrates or coenzymes on the three scFv molecules, causing them to undergo transfer or condensation reactions under the action of enzymes, thus forming stable covalent bonds and resulting in the desired triple body.

Clinical applications of Triple Body

Triple body, as a trivalent antibody with multiple targeting specificities, holds substantial potential in cancer immunotherapy by simultaneously recognizing and eliminating three different cell types. Currently, three triple body drugs have been approved worldwide, namely Emabody and Trixobody, primarily targeting hematological malignancies and achieving potent tumor-killing effects by simultaneously activating T cells, NK cells and recognizing tumor-associated antigens. These drugs are indicated for B-cell acute lymphoblastic leukemia, Hodgkin lymphoma and multiple myeloma, primarily for relapsed or refractory patients. The introduction of these drugs has introduced new treatment options in the clinic and provided crucial data and experience for the development of triple bodies.

At present, numerous triple body drugs are undergoing clinical trials at different stages, covering various diseases such as acute myeloid leukemia, solid tumors, HIV infection, non-Hodgkin lymphoma and chronic lymphocytic leukemia. The target selection of these drugs is also diverse and innovative, including HER2, EGFR, CCR5, CD37 and CD47. The clinical trial data of these drugs will provide additional evidence and support for the safety, efficacy and mechanisms of triple body.

References

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