Optimizing a lupus autoantibody for targeted cancer therapy
PW Noble, G Chan, MR Young, RH Weisbart… - Cancer research, 2015 - AACR
PW Noble, G Chan, MR Young, RH Weisbart, JE Hansen
Cancer research, 2015•AACRThe specificity of binding by antibodies to target antigens is a compelling advantage to
antibody-based cancer therapy, but most antibodies cannot penetrate cells to affect
intracellular processes. Select lupus autoantibodies penetrate into cell nuclei, and the
potential for application of these antibodies in cancer therapy is an emerging concept. Here,
we show that a divalent lupus anti-DNA autoantibody fragment with enhancing mutations
that increase its ability to penetrate cell nuclei and bind DNA causes accumulation of DNA …
antibody-based cancer therapy, but most antibodies cannot penetrate cells to affect
intracellular processes. Select lupus autoantibodies penetrate into cell nuclei, and the
potential for application of these antibodies in cancer therapy is an emerging concept. Here,
we show that a divalent lupus anti-DNA autoantibody fragment with enhancing mutations
that increase its ability to penetrate cell nuclei and bind DNA causes accumulation of DNA …
Abstract
The specificity of binding by antibodies to target antigens is a compelling advantage to antibody-based cancer therapy, but most antibodies cannot penetrate cells to affect intracellular processes. Select lupus autoantibodies penetrate into cell nuclei, and the potential for application of these antibodies in cancer therapy is an emerging concept. Here, we show that a divalent lupus anti-DNA autoantibody fragment with enhancing mutations that increase its ability to penetrate cell nuclei and bind DNA causes accumulation of DNA double-strand breaks in and is highly and selectively toxic to cancer cells and tumors with defective homology-directed repair of DNA double-strand breaks. These findings provide proof of principle for the use of optimized lupus autoantibodies in targeted cancer therapy. Cancer Res; 75(11); 2285–91. ©2015 AACR.
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