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2016 ; 291
(37
): 19661-73
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Chemically Programmed Bispecific Antibodies in Diabody Format
#MMPMID27445334
Walseng E
; Nelson CG
; Qi J
; Nanna AR
; Roush WR
; Goswami RK
; Sinha SC
; Burke TR Jr
; Rader C
J Biol Chem
2016[Sep]; 291
(37
): 19661-73
PMID27445334
show ga
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.