2020
DOI: 10.1016/j.celrep.2020.108542
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Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment

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Cited by 43 publications
(30 citation statements)
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“…A second possible engineering strategy to further elevate tumor specificity is to incorporate tumor-specific antigen binding. Mimoto and coworkers recently presented an antibody that bound hIL-6R only in the presence of ATP, which is found in high concentrations in the tumor microenvironment (TME), but only in low concentrations in healthy tissue (98). An additional method to elevate tumor specificity is to incorporate pH-responsive binding modalities into the antibody (99).…”
Section: Discussionmentioning
confidence: 99%
“…A second possible engineering strategy to further elevate tumor specificity is to incorporate tumor-specific antigen binding. Mimoto and coworkers recently presented an antibody that bound hIL-6R only in the presence of ATP, which is found in high concentrations in the tumor microenvironment (TME), but only in low concentrations in healthy tissue (98). An additional method to elevate tumor specificity is to incorporate pH-responsive binding modalities into the antibody (99).…”
Section: Discussionmentioning
confidence: 99%
“…One novel subclass of tetherbody-like multispecific biotherapeutics drugs is the condition-activated tetherbody that can enrich the active drugs in a particular location through the design of conditional activation. The conditional activation mechanisms take advantage of special conditions in tumor microenvironment such as increased levels of specific proteases [184], ATP [185,186], and others [20]. Because the presence of tumor antigen in healthy tissues can cause on-target toxicity by ADCs or bsTCEs, Probodies TM (CytomX) with a protease-cleavable peptide linker and a masking peptide can presumably remain inert until proteolytically activated locally in disease tissues [184].…”
Section: Tetherbodiesmentioning
confidence: 99%
“…Since adenosine is produced from extracellular ATP, counteracting the elevation of extracellular ATP concentration in the TME would allow initial control of adenosine formation and thus maintain effective antitumor immunity. To achieve this, Mimoto’s team generated an antibody that binds to the human IL6 receptor only when ATP concentration is increased [ 174 ]. IL6R is an attractive target protein because many cancers (colon, ovary, liver, prostate, etc.)…”
Section: Combination Of Metabolic Intervention and Immunotherapymentioning
confidence: 99%