Overcoming the On‐Target Toxicity in Antibody‐Mediated Therapies via an Indirect Active Targeting Strategy

Abstract

Antibody‐based therapies could be led astray when target receptors are expressed on nontarget sites, and the on‐target toxicity poses critical challenges to clinical applications. Here, a biomimetic indirect active targeting (INTACT) strategy is proposed based on receptor expression disparities between nontarget sites and the targets. By prebinding the antibodies using cell membrane vesicles with appropriate receptor expressions, the INTACT strategy could filter out the interactions on nontarget sites due to their inferior receptor expression, whereas ensure on‐demand release at the targets by competitive binding. The strategy is verified on CD47 antibody, realizing drastic alleviation of its clinically concerned hematotoxicity on a series of animal models including humanized patient‐derived xenograft platforms, accompanied by preferable therapeutic effects. Furthermore, the INTACT strategy proves extensive applicability for various systems including antibody, antibody–drug conjugate, and targeted delivery systems, providing a potential platform refining the specificity for frontier antibody‐related therapies.

Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma

“…One limitation of the study is that it does not include a comprehensive evaluation of the safety profile [24,62] of the compound. In particular, the novel mechanism of action of SAR442257 cannot be investigated in traditional multiple myeloma models [24].…”

Cancer Cell Membrane‐Based Materials for Biomedical Applications

“…It can filter out interactions with nontarget sites because of the expression of inferior receptors using CCM prebinding antibodies with appropriate receptor expression, offering a potential platform for improving the specificity of cutting‐edge antibody‐related therapies. [ 135 ]…”

“…It can filter out interactions with nontarget sites because of the expression of inferior receptors using CCM prebinding antibodies with appropriate receptor expression, offering a potential platform for improving the specificity of cutting-edge antibodyrelated therapies. [135] Nanomaterials could intervene in these conditions, to boost cancer immunity toward successive immunotherapeutics. The precise control of bioactive chemical release is a crucial factor in enhancing the therapeutic efficacy of CCM-NPs while simultaneously mitigating their toxicity and adverse effects.…”

Nanosystem Delivers Senescence Activators and Immunomodulators to Combat Liver Cancer

“…[ 6 ] Researchers have found that inhibiting CD47 can be effective in treating cancer. [ 7 , 8 , 9 ] The effectiveness of immunotherapy depends on the immune status of patients with HCC, and immunotherapy often needs to be combined with other treatments. [ 10 , 11 ] Combination treatment with CD47 monoclonal antibodies and PD‐1 monoclonal antibodies effectively inhibits the cancer.…”