Antibody effector mechanisms.
| Effectors Intrinsic to Antibodies . | Comment . | |
|---|---|---|
| * All require entry into cell to work; all capable of single cell kill | ||
| +All potentially immunogenic in humans | ||
| Complement | Affected greatly by antibody isotype and species, and antigen density. Resistance occurs. Reduced by antigen-antibody internalization (modulation). | |
| Antibody dependent cellular cytotoxicity (ADCC): NK, Macrophage, PMNs | Requires certain isotypes and adequate ratios of effector cells to target cells. Also reduced by modulation. | |
| Receptor-based signaling | Dependent on antigen target; may require cross-linking; effects may be additive with other drugs. | |
| Radiation Emitters From Conjugated Isotopes | ||
| Gamma rays | Poorly cytotoxic; long ranged; used for imaging. Many isotopes available; inexpensive. | |
| Beta particles | Weakly cytotoxic necessitating killing by a field effect; better for bulkier tumors or regions (e.g., bone marrow); significant bystander killing including normal or malignant cells; inexpensive, widely available isotopes produce betas. | |
| Alpha particles | High energy, short ranged (high linear energy transfer [LET]), heavy helium nuclei capable of killing single cells or small clusters of cells; minimal bystander killing; expensive and less widely available isotopes. | |
| Auger electrons | Low energy, short ranged, electrons (l μM range); capable of single cell kill, requires internalization and weakly potent. Inexpensive, widely available isotopes produce augers. | |
| Conjugated Cytotoxin* | Subclass (Example) | |
| Drug | Chemotherapies (Calicheamicin) | Minimal effects on pharmacology and immunogenicity of antibody; modest potency; subject to drug resistance mechanisms. |
| Toxins+ | Ribosomal inhibitory proteins (RIP). Heterodimer (ricin) | A-B chain heterodimers. Extremely toxic; blockade of toxin binding, B chain necessary. |
| RIP: hemitoxin (ricin A chain) | Binding site (B chain) removed, allowing less toxic use. | |
| RIP: Single chain toxin (gelonin) | Monomeric toxin; far less toxic when unconjugated from antibody. | |
| RIP: fusion toxin Ig (Pseudomonas exotoxin A fusion [FvPE]) | Truncated monomeric toxin (PE) genetically fused to truncated Ig (Fv) forming small targetable toxin. | |
| Effectors Intrinsic to Antibodies . | Comment . | |
|---|---|---|
| * All require entry into cell to work; all capable of single cell kill | ||
| +All potentially immunogenic in humans | ||
| Complement | Affected greatly by antibody isotype and species, and antigen density. Resistance occurs. Reduced by antigen-antibody internalization (modulation). | |
| Antibody dependent cellular cytotoxicity (ADCC): NK, Macrophage, PMNs | Requires certain isotypes and adequate ratios of effector cells to target cells. Also reduced by modulation. | |
| Receptor-based signaling | Dependent on antigen target; may require cross-linking; effects may be additive with other drugs. | |
| Radiation Emitters From Conjugated Isotopes | ||
| Gamma rays | Poorly cytotoxic; long ranged; used for imaging. Many isotopes available; inexpensive. | |
| Beta particles | Weakly cytotoxic necessitating killing by a field effect; better for bulkier tumors or regions (e.g., bone marrow); significant bystander killing including normal or malignant cells; inexpensive, widely available isotopes produce betas. | |
| Alpha particles | High energy, short ranged (high linear energy transfer [LET]), heavy helium nuclei capable of killing single cells or small clusters of cells; minimal bystander killing; expensive and less widely available isotopes. | |
| Auger electrons | Low energy, short ranged, electrons (l μM range); capable of single cell kill, requires internalization and weakly potent. Inexpensive, widely available isotopes produce augers. | |
| Conjugated Cytotoxin* | Subclass (Example) | |
| Drug | Chemotherapies (Calicheamicin) | Minimal effects on pharmacology and immunogenicity of antibody; modest potency; subject to drug resistance mechanisms. |
| Toxins+ | Ribosomal inhibitory proteins (RIP). Heterodimer (ricin) | A-B chain heterodimers. Extremely toxic; blockade of toxin binding, B chain necessary. |
| RIP: hemitoxin (ricin A chain) | Binding site (B chain) removed, allowing less toxic use. | |
| RIP: Single chain toxin (gelonin) | Monomeric toxin; far less toxic when unconjugated from antibody. | |
| RIP: fusion toxin Ig (Pseudomonas exotoxin A fusion [FvPE]) | Truncated monomeric toxin (PE) genetically fused to truncated Ig (Fv) forming small targetable toxin. | |