From: Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics
EarlierBsMab | NewerBsMab |
---|---|
Produced by oxidative recombination, chemical cross-linking, and enzymatic digestion of desired antibodies to yield Fab fragments which are then combined via bifunctional reagents to form a heterodimer21,22. | Produced by advanced techniques such as controlled Fab-arm exchange (cFAE), improvised somatic fusion of two hybridoma cell lines (quadroma), small molecule-antibody conjugation, genetic engineering using molecular cloning technology20. |
Inability to produce large quantities | Shorter processing time and ability to produce in large-scale. |
Rapid destruction of murine antibody fragments | Stability and longer half-life. |
Difficult to purify | > 90% pure |
Examples: MDX-21023 (targeting Her2, and CD 64 or FcyRI which is expressed on monocytes, macrophages and activated neutrophils; MDX-447 24(targeting EGFR and CD 64; HRS-3/49- Targeting CD 30 on Reed Sternberg cells in Hodgkin lymphoma and FcyRIII or CD 16 on natural killer cells and macrophages. | Examples: Catumaxomab and Solitomab (targeting EpCAM expressed on breast, ovarian and other cancer cells as well as CD3 on T cells-bispecific T cell engager or BiTE)23,26,27; Blinatumomab28(binding to both CD19 on B cell cells and CD3 on T cells). |