Antibody-drug conjugates: Recent advances in payloads

Antibody‒drug conjugates (ADCs), which combine the advantages of monoclonal antibodies with precise targeting and payloads with efficient killing, show great clinical therapeutic value. The ADCs' payloads play a key role in determining the efficacy of ADC drugs and thus have attracted great attention in the field. An ideal ADC payload should possess sufficient toxicity, low immunogenicity, high stability, and modifiable functional groups. Common ADC payloads include tubulin inhibitors and DNA damaging agents, with tubulin inhibitors accounting for more than half of the ADC drugs in clinical development. However, due to clinical limitations of traditional ADC payloads, such as inadequate efficacy and the development of acquired drug resistance, novel highly efficient payloads with diverse targets and reduced side effects are being developed. This perspective summarizes the recent research advances of traditional and novel ADC payloads with main focuses on the structure-activity relationship studies, co-crystal structures, and designing strategies, and further discusses the future research directions of ADC payloads. This review also aims to provide valuable references and future directions for the development of novel ADC payloads that will have high efficacy, low toxicity, adequate stability, and abilities to overcome drug resistance.

The interrelationships between serum HDL subpopulations and triacyglycerol / 中国病理生理杂志

AIM: To Study the influence of plasma TG level on the contents of serum HDL subpopulations. METHODS: Classified by the contents of serum TG, the serum level of HDL subpopulations in 106 normal TC and 183 high TC subjects were analyzed by two-dimensional gel electrophoresis coupled with immunodection method. RESULTS: The apo-AⅠcontents of per-?_1-HDL, HDL_~3c , HDL_~3b and HDL_~3a were higher in a certain extent in TC high subjects vs corresponding TC desirable subjects. The apo-AⅠ contents of per-?_1-HDL (in borer-line high TG subgroup) and HDL_~3b (in very high TG subgroup) were significantly higher (P

Relationship of subclasses of serum HDL and Apo A-Ⅰ gene polymorphism in hyperlipidemia / 中国病理生理杂志

AIM: To investigate apolipoprotein A-Ⅰ gene (Apo A-Ⅰ) polymorphism and its relationship with serum HDL subclasses in patients with hyperlipidemia (HL). METHODS: Apo A-Ⅰ genotype was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 118 patients with hyperlipidemia and 109 healthy subjects were determined by two-dimensional gel electrophoresis conjunction with immunodetection method. RESULTS: Both in HL group and the control group, G/G and C/C genotypes were the most frequent at -78 bp and +83 bp of Apo A-Ⅰ gene, respectively. The frequency of rare A allele at -78 bp in HL group was significantly higher than that in control group. In HL group, subjects with G/A mutation had higher serum levels of TG, Apo C-Ⅲ, pre ?_1-HDL and HDL_ 3a , and lower levels of HDL_ 2a and HDL_ 2b compared to the subjects with G/G genotype. CONCLUSION: The G/A transition in the -78 bp position of the Apo A-Ⅰ gene promoter in patients with hyperlipidemia is associated with HDL subclasses. There is a general shift toward smaller sized HDL, which, in turn, indicates that HDL maturation might be abnormal.

Relationship between HDL subclasses and TC/HDL-C, TG/HDL-C ratio / 中国病理生理杂志

2.2 in serum, the particle size of HDL shifted towards smaller sizes, which indicates that reverse cholesterol transport might be weakened and HDL maturation might be abnormal.