Antibodies immunocytokines

Immunocytokines Antibody or antibody fragment Cytokine, interleukin or growth factor aEpCAM-IL-12 aHer2/weM-IL-12 RM4-TNFa RM4-IFNy [119] [120] [121] [122]... 

A variant of the original immunotoxin approach is the so-called immunocytokines. In these constructs the antibody targeting moiety is maintained, but the toxin as the effector molecule is replaced by a cytokine. In contrast to toxins, cytokines are often proteins endogenously produced in man. If both the antibody and cytokine are of human origin, then no foreign proteins are introduced which could provoke an antibody response from the host immune system when the drug targeting preparation is clinically applied. 

Figure 11.6. Schematic diagram showing the assembly of IL-12 protein for antibody-based drug delivery, (a) The mature sequences of the p35 subunit of IL-12 are fused to the C-terminus of the heavy chain of a tumour-specific antibody and co-expressed with the antibody light chain and the p40 subunit of IL-12. Formation of the final immunocytokine requires the creation of disulfide bridges between the antibody chains and interactions of p35 and p40 subunits of IL-12 [119]. (b) Alternatively the IgG heavy chain and both subunits of IL-12 can be linked via flexible linkers allowing for equimolar assembly of IL-12 [120].

---