Table 6.
Comparison of strategies to target the inside of cells with antibodies
| Properties | Intrabody expression | Antibody delivery (as a protein) | ||
|---|---|---|---|---|
| Cytosol/nucleus | ER/mitochondria | Cytosol/nucleus | Other compartments | |
| Correct antibody folding possible? | ? | + | + | + |
| Epitope choice: can non-neutralizing antibodies be used? |
– (+ if combined with targeted degradation) |
+ |
– (+ if combined with targeted degradation) |
– (+ if combined with targeted degradation) |
| Antibody-mediated functional knockdown | + | + | + | ? |
| Targeted degradation? | Tags targeting for proteasomal degradation | ER: targeting for ERAD | TRIM21 for antibodies with Fc part, tags targeting for proteasomal degradation | Lysosomal targeting (e.g. LYTACs) |
| Examples of special features targeted | PTMs, individual domains, conformations | Complex formation, knockdown in selected cellular compartment | Long half-life protein degraded, tracking of unmodified endogenous POIs | |
| Deliverable in therapy? | Adoptive cell therapy, gene therapy | Adoptive cell therapy, gene therapy |
Adoptive cell therapy? Local tissue electroporation? |
+ (ADCs, approved for therapy) |
ADCs antibody–drug conjugates, ER endoplasmic reticulum, ERAD ER-associated degradation, LYTACs lysosome-targeting chimaeras, POIs proteins of interest, PTM post-translational modification, TRIM21 tripartite motif containing-21,? indicates to be determined, – indicates no, + indicates yes