In the past few decades, monoclonal drugs have had huge applications in diagnosis, treatment and drug targeting. The diagnosis of any infectious disease usually requires proof of the pathogen or specific antibodies against the pathogen or its toxin. In some infectious diseases, such as reproductive or respiratory infections, the pathogen can appear throughout the infection process, while for other infectious diseases, it can be seen in a short period of time. Tests based on specific antibodies can identify disease-related pathogens or the toxins they secrete or any other proteins they may unintentionally release. Monoclonal antibodies can develop unique epitopes that recognize pathogens/toxins. MAb can recognize a single antigenic determinant feature of a pathogen. This limited reactivity allows precise identification of the organism of interest, which is the main advantage of monoclonal antibodies over polyclonal antisera.
The diagnostic and therapeutic properties of monoclonal antibodies utilize the unparalleled specificity of monoclonal antibodies. Once the correct target antigen is determined, monoclonal antibodies against the antigen/antigenic determinant can be produced. This monoclonal antibody can be used for diagnostic or therapeutic purposes. Once injected, this antibody will be built into a specific target cell instead of a large number of other cells. Monoclonal antibodies can be used alone (naked monoclonal antibodies) to trigger the desired response, or they can be linked to toxic loads such as radioisotopes or toxins or drugs/prodrugs (conjugated antibodies) to produce the desired effect.
Monomethyl auristatin E (MMAE, vedotin) is a very effective anti-mitotic agent, which inhibits cell division by blocking the polymerization of tubulin. Clinical studies have found that monomethyl auristatin E or MMAE is 100-1000 times more potent than adriamycin (Adriamycin/Rubex), and has a super cytotoxic microtubule inhibitor. Therefore, it cannot be used as a medicine by itself. However, as part of an antibody-drug conjugate (ADC) or ADC, MMAE can specifically recognize the expression of specific markers in cancer cells by linking with monoclonal antibodies (mAb) and guide MMAE to specific targeted cancer cells .
ADC is a new type of therapeutic agent, which consists of monoclonal antibodies (mAb) covalently bound to cytotoxic drugs through chemical linkers. mAbs preferentially target cell surface antigens that are overexpressed in tumor cells. After binding, ADC is internalized by tumor cells, where it undergoes lysosomal degradation, resulting in the release of cytotoxic drugs. The use of targeted delivery of highly effective cytotoxic drugs aims to enhance anti-tumor activity while minimizing the toxicity to normal tissues. In addition, this treatment method utilizes the advantageous pharmacokinetic (PK) properties of antibodies to provide sustained delivery of cytotoxic drugs.
Many ADCs in clinical development use protease-labile dipeptide linkers (valine-citrulline [vc]) to couple the thiol present in mAb cysteine (vc-MMAE ADC) to monomethyl MMAE United. In 2011, the US Food and Drug Administration approved a vc-MMAE ADC, brentuximab vedotin (ADCETRIS™) for the treatment of recurrent anaplastic large cell lymphoma and Hodgkin’s lymphoma.
In the past decade, a variety of vc-MMAE ADCs have been developed for different targets and different tumor indications, which provides a unique opportunity to characterize the clinical pharmacology of such ADCs. The researchers connected the MMAE to the monoclonal antibody through a linker. The linker connecting the two is stable in the extracellular fluid, but once the antibody-drug conjugate binds to the targeted cancer cell antigen and enters the cancer cell, it will be cleaved by cathepsin, after which the ADC releases toxic MMAE and activates it effectively The anti-mitotic mechanism. Antibody-drug conjugates enhance the anti-tumor effect of antibodies and reduce the adverse systemic effects of highly effective cytotoxic drugs.