From: Targeted drug delivery for cancer therapy: the other side of antibodies
Item | Antibodies (full length) | Peptides |
---|---|---|
Discovery of novel cell surface targets | Most approved TMAs do not target TSAs; for traditional mAbs target must be antigenic; screening selects mAbs to dominant epitopes; mAb specs depend on strain mouse/rat used | Target does not need to be antigenic; no prior knowledge of target molecule needed |
Generation technology | Traditionally via murine hybridoma, then humanization; humanized mouse; via phage scFv phage display then grafting to Ig backbone | Combinatorial DNA, RNA, peptide library phage or cell based display technologies (random or scFv based); Combinatorial chemistry |
Molecular structure | Standard Ab unit; different Ig isotypes; bispecific Ab; multi-bodies | Linear; cyclic; scFv; non natural amino acids; novel small molecules |
Intracellular transport | Not a selection criteria of currently approved TMAs; technically difficult to select during screening | Screening technologies allow for easy selection of candidates that induce rapid endocytosis |
Pharmacodynamics and Pharmacokinetics | Non-linear, depends of many variables, difficult to predict | Smaller molecular mass; larger formulation knowledge base for designed PD and PK |
Conjugation of carrier to drug (for ADC or PDC) | Only ~50% mAb bound to drug; difficult to predict mAb/drug stoichiometry and drug position; conjugation chemistry limited to aqueous solutions. | Enhanced flexibility in conjugation chemistry for coupling to linker and drug, allowing wider selection of drugs including non-water soluble compounds, synthesis in organic solvents and aqueous solutions ; scaffolds available for conjugation to different drugs; formation of metal complexes; defined and predictable products; |
Antigenicity of final product | Depends of extent of humanization. | Negligible |
Bystander immune effector function | ADCC; CDC; CTL?; | None |
Tumor penetration | Limited in solid tumors | Enhanced |
Manufacture/Quality Control | Structure of ADC heterogeneous; high upstream development, cell culture, bioreactor design) and downstream ( purification) costs | Significantly lower production costs (up to ~35 amino acids); increased product reproducibility |