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Table 2 Production, limitations, and examples of first and subsequent generations of BsMab

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).