Peptide-drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.

Peptide-drug conjugates for tumor targeted diagnosis and treatment / 药学学报

Cancer is still one of the major diseases threatening human life and health. At present, how to achieve precise diagnosis and treatment of tumors is the biggest challenge in cancer treatment. Prodrugs use the tumor specificity of targeting molecules to deliver anticancer drugs to tumor sites, which can effectively improve drug bioavailability, therapeutic efficacy and safety, and are currently a hot spot in the research and development of anticancer drugs. The targeting molecules of prodrugs mainly include nucleic acid aptamers, polymers, antibodies, polypeptides, etc. Among them, polypeptides have the advantages of good biocompatibility, controllable degradation performance, high in vivo responsiveness, and simple and easy preparation methods, and are widely used. It is used to construct peptide-drug conjugates (PDC) prodrugs to achieve targeted therapy of tumors. In recent years, with the development of phage peptide library technology and peptide standard solid-phase synthesis technology, more and more targeted peptides have been discovered and effectively synthesized and modified, providing strong support for the development of PDC. This review briefly introduces the types and functions of functional peptides and linkers in PDC, and discusses the application of PDC in chemotherapy, immunotherapy and photodynamic therapy in tumor targeted diagnosis and treatment, and finally summarizes the difficulties faced by PDC drug development.

Preparation and characterization of a recombinant poly-epitopic vaccine EgG1Y162-2 (4) against cystic echinococcosis based on the linker GSGGSG / 中国血吸虫病防治杂志

Objective To perform prokaryotic expression and preliminary characterization of the recombinant poly-epitope vaccine EgG1Y162-2 (4) against cystic echinococcosis. Methods The recombinant poly-epitope vaccine EgG1Y162-2 (4) against Echinococcus granulosus based on the linker GSGGSG was subjected to structural three-dimensional (3D) modeling using immunoinformatics to analyze the structural changes and evaluate the antigenicity of the vaccine. The pET30a-EgG1Y162-2 (4) recombinant plasmid was generated using double digestion with EcoR I and Sal I, and then transformed into competent cells. Following protein induction with isopropyl-β-D-thiogalactoside (IPTG), the prokaryotic expression proteins were characterized using Western blotting, and the antigenicity of the recombinant protein was analyzed using sera from cystic echinococcosis patients and health volunteers. Results The four EgG1Y162-2 proteins coupled by the 3D structure of the recombinant vaccine EgG1Y162-2 (4) presented independent and effective expression and good antigenicity. The highest protein expression was detected in the supernatant following induction of the recombinant plasmid pET30a-EgG1Y162-2 (4) by 0.2 mmol/L IPTG at 37 °C for 4 h, and a pure protein component was seen following elution with 60 mmol/L imidazole. Western blotting analysis of the recombinant multiepitope protein HIS-EgG1Y162-2 (4) showed a band at approximately 39 kDa, and this band was recognized by sera from cystic echinococcosis patients. Conclusion A recombinant poly-epitope vaccine EgG1Y162-2 (4) against cystic echinococcosis has been successfully constructed, which provides a preliminary basis for researches on recombinant multi-epitope vaccine against cystic echinococcosis.

Cyclization of α-conotoxin A10LPnIA with lysine assisted cyanuric chloride linker / 药学学报

The cyanuric chloride linkers have been used for cyclizing polypeptide, but not used for α-conotoxin, the peptides with rich disulfide bonds and more amino acid residues. In this study, cyclic peptides c[A10L]PnIA-1-4 were synthesized efficiently by lysine assisted cyanuric chloride linkers with 28.92%-52.00% yields. The activity evaluation showed that the IC50 values of c[A10L]PnIA-1 against α7 and α3β2 nAChR subtypes were 5 and 7 times higher than [A10L]PnIA respectively, and the subtype selectivity was maintained. The results of circular dichroism show that this cyclization method had no significant effect on its secondary structure. Compared with the commonly used head-to-tail cyclization in conotoxin cyclization, this method has the advantages of rapid reaction and high yield, which is expected to be further applied to the cyclization study of various α-conotoxins.

Advances in the optimization of the linker in proteolysis-targeting chimeras (PROTAC) / 药学学报

With high selectivity and potency, target protein degradation technology has recently emerged as a strategy for drug discovery and design. Proteolysis-targeting chimeras (PROTAC) function as inducers for the degradation of target proteins and are a research focus in drug development. Current research on PROTAC mainly revolves around the rational design of PROTAC molecules, the discovery of new E3 ubiquitin ligase ligands and improvement in drug targeting. In this review, we focus on the PROTAC linker and its effects on the generation of the E3 enzyme-PROTAC-target protein ternary complex from three standpoints: length, binding site and chemical properties. We discuss the influences of the linker on the efficacy and the selectivity of PROTAC molecules.

Antibody-drug conjugates: Recent advances in linker chemistry

Antibody-drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody-drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers.

Role of nucleosome positioning in 3D chromatin organization and loop formation

We present a physics-based polymer model that can investigate 3D organization of chromatin accounting for DNA elasticity,DNA-bending due to nucleosomes, and 1D organization of nucleosomes along DNA. We find that the packing density ofchromatin oscillates between densities corresponding to highly folded and extended configurations as we change thenucleosome organization (length of linker DNA). We compute the looping probability of chromatin and show that thepresence of nucleosomes increases the looping probability of the chain compared to that of a bare DNA. We also show thatlooping probability has a large variability depending on the nature of nucleosome organization and density of linker histones.

Consideration of antibody drug conjugates development and regulation / 药学学报

Antibody drug conjugates (ADCs), as they combine the targetability of monoclonal antibody and cytotoxicity of small molecules, are a growing class of therapeutics for cancer. The key factor of ADCs development is the accurate selection of parameters including tumor target, monoclonal antibody, cytotoxic payload, and linkage strategy of antibody to payload. Here, we summarize the main elements in the structural design and the development of ADCs, as well as the regulatory consideration of product manufacturing and control, which would be helpful for the research and development of ADCs.

Recent advances in construction of small molecule-based fluorophore-drug conjugates / 药物分析学报

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs' transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.

Modification Of Gums By Periodate Oxidation: A Natural Cross-Linker

Scientists throughout the world are in search of novel modified biopolymer to fabricate smart drug delivery systems based on hydrogel formulations using several cross-linkers like glutaraldehyde, glyoxal, epichlorhydrin, adipic acid dihydrazide, carbodiimide, genipin, etc. Agents that are fused into the polymeric structure like isocyanates, glutaraldehyde, polyepoxides, etc., and are extremely toxic in nature. In addition, these are susceptible to percolate out into the body on biodegradation of polymeric structure. As an alternative to these toxic cross-linking agents, the periodate-Schiff base staining technique is widely being used for cross-linking in biology and biochemistry. The mechanism of this cross-linking technique is based on the reaction in-between the Schiff reagent and the aldehydes produced via the periodate oxidation. During the past few decades, several researchers have already been studied on the natural gums and also, developed their dialdehyde derivatives via the periodate oxidation technique. These periodate oxidized gums are being used to cross-link gelatin, other proteins and chitosan to develop various smart systems for drug delivery, tissue engineering, wound dressing, edible films, etc. The current review presents a comprehensive discussion of the available reported literature on the periodate oxidation of various gums and their use as natural cross-linker.

Advanced research and technology development of antibody-drug conjugates / 药学学报

Although numbers of naked antibodies showing clinical efficacy as single agents, their therapeutic effect is limited. Chemotherapy is very effective but with relatively large side effects, so conjugation of small chemotherapeutic drugs to antibodies is one of the important methods to enhance therapeutic potential of antibodies. Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of chemotherapeutic drugs. These modified antibodies are expected to selectively deliver chemotherapeutic drugs to tumor cells and provide sustained clinical benefit to cancer patients, at the same time, minimizing systemic toxicity. ADCs are expected to bring together the benefits of highly potent drugs on the one hand and selective binders of specific tumor antigens on the other hand. However, designing an ADC is very complex, requiring thoughtful combination of antibody, linker, and payload drugs in the context of a target and a defined cancer indication. Although many challenges remain, recent clinical success has generated intense interest in this therapeutic class.

Structure and function of B-cell linker and its role in the development of B cell-related diseases / 南方医科大学学报

B cell linker (BLNK) is a key linker protein of B cell receptor (BCR) signaling pathway. BLNK participates in the regulation of PLC-γactivity and the activation of Ras pathway through its typical structure and interaction network with other proteins, and is thus widely involved in the regulation of B cell proliferation, differentiation, apoptosis and signal transduction. Furthermore, it is closely related to anaphylactic diseases, multiple sclerosis, chromosomal aneuploidy, aneuglobulinemia, B lymphocytic leukemia and lymphoma. Herein we review the structure and biological function of BLNK and its role in B cell-related diseases. BLNK can cooperate with a series of effective proteins to activate BCR signaling pathway, thereby regulating the development, maturation and function of B cells. The functional mutation of BLNK can destroy the homeostasis of B cells and affect the development and maturation of B cells, which leads to the occurrence of B cell related diseases. A comprehensive understanding of the biological functions of BLNK not only provides insights into the pathogenesis of B cell-related diseases, but also inspires new ideas and helps to find breakthroughs for the treatment of these diseases with BLNK as the therapeutic target.

Histone variants: critical determinants in tumour heterogeneity / 医学前沿

Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

Activación de la célula T, alteraciones en el lupus eritematoso sistémico, una revisión narrativa / T-cell activation, alterations in systemic lupus erythematosus: A narrative review

Resumen La activación de los linfocitos T se inicia a través de la presentación de antígenos endógenos o exógenos por células presentadoras de antígenos a través del complejo mayor de histocompatibilidad, el cual se une a un receptor especializado presente en los linfocitos T. Este reconocimiento desencadena una cascada de señalización intracelular que conlleva a un aumento en la expresión de integrinas, modificaciones del citoesqueleto y producción de factores de transcripción involucrados en la liberación de citocinas y mediadores inflamatorios. Uno de los inductores más importantes en la activación celular es el complejo enzimático con acción tirosina cinasa. Las cinasas que pertenecen a la familia SRC (SFK), FYN y LCK están involucradas en un gran número de procesos importantes en la activación, modulación de la respuesta linfocitaria y el desarrollo de enfermedades autoinmunes. La regulación de la señalización de las cinasas, así como de proteínas adaptadoras involucradas en la activación del linfocito T, son fundamentales para mantener el umbral de activación y modulación de la respuesta del linfocito. La fosforilación de sitios de regulación positiva de estas proteínas es importante para permitir una configuración activa de la proteína y de esta forma su máxima capacidad como cinasa. La fosforilación de los sitios de regulación negativa conlleva a una configuración cerrada de la proteína de tal forma que reduce su función de cinasa e inhibe su función. Las alteraciones en la señalización por modificación de algunas proteínas citoplasmáticas se asocian en algunos casos al desarrollo de enfermedades autoinmunes, como el lupus eritematoso sistémico. En condiciones fisiológicas, el complejo receptor de linfocitos T se reagrupa con complejos proteicos que interactúan armónicamente para generar una sen al interna. Los eventos de señalización alterados son en parte los responsables de una expresión anómala de citocinas, entre ellas la interleucina-6 (IL-6), IL-10, IL-2, IFN y CD40 ligando; estas modificaciones alteran la capacidad de los linfocitos T para sobre estimular a los linfocitos B, traduciéndose en un aumento en la producción de autoanticuerpos y en el desencadenamiento de la enfermedad autoinmune.

Abstract The activation of T cells is initiated by the presentation of exogenous or endogenous antigens, by antigen presenting cells through the major histocompatibility complex, which binds to a special receptor on T cells. This acknowledgement triggers a cascade of intracellular signalling that leads to an increase in integrin expression, cytoskeletal modifications, and transcription factors production involved in the liberation of cytokines and inflammatory mediators. One of the most important inducers in cell activation is the enzymatic complex with tyrosine kinase action. The kinases which belong to the SRC (SFK) LCK and FYN family have been involved in a large number of important processes in the activation and modulation of the T cells response, as well as in the development of autoimmune diseases. Regulating the kinases signalling, as well as the adapter proteins involved in T cell activation, is essential for maintaining an activation threshold, as well as the modulation of cell response. The phosphorylation of the positive regulation sites of these proteins is important to allow an active configuration of the protein and thereby its maximum capacity as kinase. The phosphorylation of negative regulation sites leads to a closed configuration of the protein that reduces its kinase function, and thereby inhibits its own function. The alteration in signalling by the modification of certain cytoplasmic proteins in some cases is associated with the development of autoimmune diseases, such as systemic lupus erythematosus. Under physiological conditions the T cell receptor complex regroups with protein complexes that interact harmonically to generate an internal signal. The altered signalling events are partly responsible for an anomalous expression of cytokines, including the interleukin-6 (IL-6), IL-10, IL-2, IFN, and CD40 linking, these modifications affects the cells ability to over-stimulate T and B cells, resulting in an increased production of autoantibodies and the triggering of the autoimmune disease.

Antibody-drug conjugates: recent advances in conjugation and linker chemistries

The antibody-drug conjugate (ADC), a humanized or human monoclonal antibody conjugated with highly cytotoxic small molecules (payloads) through chemical linkers, is a novel therapeutic format and has great potential to make a paradigm shift in cancer chemotherapy. This new antibody-based molecular platform enables selective delivery of a potent cytotoxic payload to target cancer cells, resulting in improved efficacy, reduced systemic toxicity, and preferable pharmacokinetics (PK)/pharmacodynamics (PD) and biodistribution compared to traditional chemotherapy. Boosted by the successes of FDA-approved Adcetris and Kadcyla, this drug class has been rapidly growing along with about 60 ADCs currently in clinical trials. In this article, we briefly review molecular aspects of each component (the antibody, payload, and linker) of ADCs, and then mainly discuss traditional and new technologies of the conjugation and linker chemistries for successful construction of clinically effective ADCs. Current efforts in the conjugation and linker chemistries will provide greater insights into molecular design and strategies for clinically effective ADCs from medicinal chemistry and pharmacology standpoints. The development of site-specific conjugation methodologies for constructing homogeneous ADCs is an especially promising path to improving ADC design, which will open the way for novel cancer therapeutics.

Effects of Dianxianqing Granule on the IL-6 Content and GFAP,Iba-1 Expressions in Hippocampus Tis-sue of Rats with Kainate-induced Epilepsy / 中国药房

OBJECTIVE:To study the effects of Dianxianqing granule on the interleukin(IL-6)content and glial fibrillary acid-ic protein(GFAP),ionized calcium linker molecules 1(Iba-1)expressions in hippocampus tissue of rats with kainate-induced epi-lepsy,and explore its mechanism of preventing and treating epilepsy. METHODS:Rats were randomly divided into sham operation group (distilled water),model group (distilled water),phenytoin group (0.03 g/kg,positive control) and Dianxianqing granule low-dose,medium-dose,high-dose groups(4.74,9.47,18.94 g/kg,calculated by crude drug),20 in each group. Rats were intra-gastrically administrated once a day,for 7 d. After 1 h of last administration,except for sham operation group,rats in other groups received single injection of kainite in hippocampus CA1 of left side to induce the epilepsy model. Behavioral changes and death of rats were observed. After 24 h of modeling,enzyme-linked immunosorbent method was used to detect the IL-6 content in hippocam-pus tissue of rats,Nissl staining was used to count the hippocampus neurons,and immunohistochemistry was used to detect the GFAP,Iba-1 expressions in hippocampus tissue of rats. RESULTS:Compared with sham operation group,rats in model group had obvious epilepsy symptoms after modeling,and parts of rats died;IL-6 content and number of neurons in hippocampus tissue were obviously decreased (P<0.01), while GFAP, Iba-1 expressions were obviously enhanced (P<0.01). Compared with model group,epilepsy symptoms and death in each administration group had improved,while IL-6 content in hippocampus tissue were in-creased to varying degrees,with no statistical significance (P>0.05). The numbers of neurons in phenytoin group,Dianxianqinggranule medium-dose, high-dose groups were obviously in-creased(P<0.01);GFAP expression was obviously decreased (P<0.01). Iba-1 expressions in hippocampus tissue in phenyt-oin group,Dianxianqing granule high-dose group were obvi-ously decreased (P<0.01). CONCLUSIONS:Dianxianqing granule can play the role in preventing and treating epilepsy by inhibiting GFAP,Iba-1 expressions in hippocampus tissue and in-creasing the number of neurons in hippocampus tissue.

Effects of Dianxianqing Granule on the IL-6 Content and GFAP,Iba-1 Expressions in Hippocampus Tis-sue of Rats with Kainate-induced Epilepsy / 中国药房

OBJECTIVE:To study the effects of Dianxianqing granule on the interleukin(IL-6)content and glial fibrillary acid-ic protein(GFAP),ionized calcium linker molecules 1(Iba-1)expressions in hippocampus tissue of rats with kainate-induced epi-lepsy,and explore its mechanism of preventing and treating epilepsy. METHODS:Rats were randomly divided into sham operation group (distilled water),model group (distilled water),phenytoin group (0.03 g/kg,positive control) and Dianxianqing granule low-dose,medium-dose,high-dose groups(4.74,9.47,18.94 g/kg,calculated by crude drug),20 in each group. Rats were intra-gastrically administrated once a day,for 7 d. After 1 h of last administration,except for sham operation group,rats in other groups received single injection of kainite in hippocampus CA1 of left side to induce the epilepsy model. Behavioral changes and death of rats were observed. After 24 h of modeling,enzyme-linked immunosorbent method was used to detect the IL-6 content in hippocam-pus tissue of rats,Nissl staining was used to count the hippocampus neurons,and immunohistochemistry was used to detect the GFAP,Iba-1 expressions in hippocampus tissue of rats. RESULTS:Compared with sham operation group,rats in model group had obvious epilepsy symptoms after modeling,and parts of rats died;IL-6 content and number of neurons in hippocampus tissue were obviously decreased (P<0.01), while GFAP, Iba-1 expressions were obviously enhanced (P<0.01). Compared with model group,epilepsy symptoms and death in each administration group had improved,while IL-6 content in hippocampus tissue were in-creased to varying degrees,with no statistical significance (P>0.05). The numbers of neurons in phenytoin group,Dianxianqinggranule medium-dose, high-dose groups were obviously in-creased(P<0.01);GFAP expression was obviously decreased (P<0.01). Iba-1 expressions in hippocampus tissue in phenyt-oin group,Dianxianqing granule high-dose group were obvi-ously decreased (P<0.01). CONCLUSIONS:Dianxianqing granule can play the role in preventing and treating epilepsy by inhibiting GFAP,Iba-1 expressions in hippocampus tissue and in-creasing the number of neurons in hippocampus tissue.

Construction of high-yield strain by optimizing lycopene cyclase for β-carotene production / 生物工程学报

To optimize key enzymes, such as to explore the gene resources and to modify the expression level, can maximize metabolic pathways of target products. β-carotene is a terpenoid compound with important application value. Lycopene cyclase (CrtY) is the key enzyme in β-carotene biosynthesis pathway, catalyzing flavin adenine dinucleotide (FAD)-dependent cyclization reaction and β-carotene synthesis from lycopene precursor. We optimized lycopene cyclase (CrtY) to improve the synthesis of β-carotene and determined the effect of CrtY expression on metabolic pathways. Frist, we developed a β-carotene synthesis module by coexpressing the lycopene β-cyclase gene crtY with crtEBI module in Escherichia coli. Then we simultaneously optimized the ribosome-binding site (RBS) intensity and the species of crtY using oligo-linker mediated DNA assembly method (OLMA). Five strains with high β-carotene production capacity were screened out from the OLMA library. The β-carotene yields of these strains were up to 15.79-18.90 mg/g DCW (Dry cell weight), 65% higher than that of the original strain at shake flask level. The optimal strain CP12 was further identified and evaluated for β-carotene production at 5 L fermentation level. After process optimization, the final β-carotene yield could reach to 1.9 g/L. The results of RBS strength and metabolic intermediate analysis indicated that an appropriate expression level of CrtY could be beneficial for the function of the β-carotene synthesis module. The results of this study provide important insight into the optimization of β-carotene synthesis pathway in metabolic engineering.

Bibliometric analysis of antibody-drug conjugates / 中国生化药物杂志

Objective To retrieve and analyze domestic and international literatures about antibody-drug conjugates, and understand the recent progress and current situation.Methods PubMed, Web of Science and CNKI were searched to collect all the literatures connected with ADCs from the beginning to January, 2016.Endnote X7 was used to sort out and summarize.The type of literature, published year, first author, research institution, published journal, cited frequency, research contents and patent situation were analyzed with bibliometric methods.Results A total of 645 literatures were included, among which 495 were foreign articles and 150 were Chinese articles.The literatures greatly increased after the 21st century.The top one nation and journal which published the most articles were America and Clinical Cancer Research, respectively.Krop IE and Younes A published the most articles.Among them, the most frequently cited paper was cited up to 686 times.Selection of the targets, site-specific drug conjugation to antibodies and cytotoxic agents were frequently involved.Conclusion ADCs, which have made breakthrough progress, are the focus in the field of cancer research.However, there is still room for improvement, and we still need further exploration.

Maytansine class antibody drug conjugates:research advances / 国际药学研究杂志

Compared with the traditional anti-tumor therapy,the antibody-based therapeutic strategies have shown consider?ably higher targeting selectivity and lower side effects. Antibody drug conjugates(ADC),combining the advantage of the biological antibodies and small molecule toxins,is regarded as a new way for the future cancer therapy. Maytansines are one of the cytotoxins widely used in ADC and the postmarketing ADC ado-trastuzumab emtansine(Kadcyla,ATE)which use such toxins successfully has expanded the indications from leukemia to other solid tumors. Currently,the clinical research progress in such ADC goes smoothly. This paper reviews the characteristics,metabolic characteristics,preparation of each component and the latest clinical research prog?ress in the maytansine class ADC.