Antibodies are Y-shaped proteins that bind to specific epitopes on antigens, enabling neutralization, agglutination, or immune signaling . Their efficacy depends on:
Target specificity: Binding to unique epitopes on pathogens, receptors, or proteins (e.g., AT1R, ETX) .
Isotype: Determines antibody function (e.g., IgG for neutralization, IgE for allergies) .
Cross-reactivity: Commercial antibodies may lack specificity, as seen in studies of AT1R antibodies .
Rabbit monoclonal antibodies against Clostridium perfringens epsilon toxin (ETX) were developed to neutralize pore-forming toxins :
| Property | Value |
|---|---|
| Neutralization mechanism | Block toxin binding or oligomerization |
| In vivo efficacy | Protection post-ETX exposure |
| Applications | Diagnostics, therapeutics for toxin-mediated diseases |
Neutralization: Antibodies targeting ETX oligomerization prevented endocytosis and cellular damage .
Detection methods: Western blot, ELISA, and flow cytometry validated specificity .
Commercial antibodies for angiotensin II type 1 receptor (AT1R) often lack specificity :
| Antibody Source | Observed Bands (kDa) | Specificity (Wild-type vs. KO mice) |
|---|---|---|
| Santa Cruz (sc-1173) | 43 | Non-specific (identical in WT and KO) |
| Abcam (ab18801) | 43, 50 | Non-specific |
Validation failure: None met criteria for AT1R specificity .
Recommendation: Use radioligand binding assays instead of antibodies for AT1R studies .
ATG-101: A tetravalent PD-L1×4-1BB antibody that activates antitumor immunity by blocking PD-L1 and engaging 4-1BB .
Mechanism: Cross-linking PD-L1 and 4-1BB on T cells enhances antitumor responses while reducing hepatotoxicity .
Depletion-AAVs: Adeno-associated viruses expressing lymphocyte-depleting antibodies (e.g., anti-CD4, anti-CD8) enable durable immune subset elimination .
Advantages: Avoids GEMM limitations; enables combinatorial targeting in diverse genetic backgrounds .