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The first bi-specific antibody against myeloma targeting Wue-1 on plasma cells was developed as scFv BiTE antibody. This development demonstrated killing of myeloma cell lines and primary myeloma cells in vitro at low temperature. Since then, bi-specific antibodies targeting other antigens such as CD387, CD1388, CS-110, and FcRH511 have been developed.

According to a new research report by RNCOS entitled, “Global Double Barreled Antibodies Drug Sales (BLINCYTO & Removab), Pipeline Analysis (By Phase, Technology, and Indication), & Global Market Forecasts 2022”, other strategies such as engagement of NK cells with NKG2D receptor have been explored. Currently, B-cell maturation antigen (BCMA, CD269), primarily expressed on plasma cells and involved in pro-survival signaling, has been a target with high preclinical development activities. Moreover, there are many forms of anti-BCMA bi-specific antibodies in preclinical development. Ab-957 is a BCMAxCD3 IgG like bi-specific antibody manufactured using Genmab DuoBody Technology by Janssen. This technology makes use of half-molecule exchange to generate bispecifics that are close in proximity to their natural format though with low immunogenicity. Ab-957 is being developed for Phase 1 clinical trial testing.
 
Furthermore, EM801 and EM901 (ENgMab/Celgene) are also IgG based antibodies that are bivalent to BCMA and monovalent to CD3. Synergy is seen in in-vitro myeloma cell lysis when EM901 is given in combination with lenalidomide, daratumumab, and anti-PD1 antibody. Pfizer also has developed a fully human IgG anti-BCMAxCD3 bispecific antibody.
 
One of the BiTE antibodies furthest along in clinical trial development is BI 836909 by Amgen. BI 836909 is a tandem scFv to BCMA (N-terminal) and CD3 (C-terminal). In vitro testing showed that this BiTE antibody activates T cells in a BCMA dependent manner and induces T cell proliferation and myeloma cell apoptosis in both myeloma cells. A Phase 1 clinical trial is concomitantly under way testing BI 836909 in patients with relapsed myeloma. This is a multicenter study being conducted in France and Germany and planned data analysis is to be done in Summer 2017. In lieu of such advancements in bi-specific antibody development the overall market for double barreled antibodies is expected to flourish in future.
 
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