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Chemically programmed bispecific antibodies (biAbs) endow target cell-binding small molecules with the ability to recruit and activate effector cells of the immune system. Here we report a platform of chemically programmed biAbs aimed at redirecting cytotoxic T cells to eliminate cancer cells. Two different antibody technologies were merged together to make a novel chemically programmed biAb. This was achieved by combining the humanized anti-hapten monoclonal antibody (mAb) h38C2 with the humanized anti-human CD3 mAb v9 in a clinically investigated diabody format known as Dual-Affinity Re-Targeting (DART). We show that h38C2 × v9 DARTs can readily be equipped with tumor-targeting hapten-derivatized small molecules without causing a systemic response harming healthy tissues. As a proof of concept, we chemically programmed h38C2 × v9 with hapten-folate and demonstrated its selectivity and potency against folate receptor 1 (FOLR1)-expressing ovarian cancer cells in vitro and in vivo Unlike conventional biAbs, chemically programmed biAbs in DART format are highly modular with broad utility in terms of both target and effector cell engagement. Most importantly, they provide tumor-targeting compounds access to the power of cancer immunotherapy.
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
August 2012,
The Journal of biological chemistry,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
January 2019,
Frontiers in immunology,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
April 2014,
Trends in biotechnology,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
May 2013,
Protein engineering, design & selection : PEDS,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
January 2011,
The Journal of biological chemistry,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
February 2021,
Nature reviews. Chemistry,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
August 2017,
Bioorganic & medicinal chemistry letters,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
October 2020,
Nature communications,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
May 2013,
ACS medicinal chemistry letters,
Even Walseng, and
Christopher G Nelson, and
Junpeng Qi, and
Alex R Nanna, and
William R Roush, and
Rajib K Goswami, and
Subhash C Sinha, and
Terrence R Burke, and
Christoph Rader
January 2007,
Bioorganic & medicinal chemistry letters,
