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Table 3 Comparison between full length antibodies and peptides as drug carriers in targeted drug delivery

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

  1. TSA – tumor specific antigen; mAb – monoclonal (hybridoma) antibody; scFv – single chain Fv region of antibody combining site; ADCC – Antibody dependant cellular cytotoxicity; CDC – Complement dependant cytotoxicity; CTL – Cytotoxic T-lymphocyte; Ig - Immunoglobulin.