{"entity":{"id":"bystander-effect","kind":"term","name":"Bystander effect (ADC)","aka":[],"tldr":"When a released payload leaks out of the targeted cell and kills its neighbours, including cells that lack the target.","summary":"In an antibody-drug conjugate, the bystander effect is what happens when the released payload leaks out of the targeted cell and kills neighbouring cells, including cells that lack the target. It requires a cleavable linker and a membrane-permeable payload such as DXd, MMAE or SN-38. This explains why Trastuzumab deruxtecan works in HER2-low tumours while T-DM1, whose payload is not permeable, does not, and the same leakage is a source of toxicity to adjacent normal tissue. The concept is linked to the Antibody-drug conjugate (ADC) and Topoisomerase-I inhibitors technologies and to the payload terms DXd, MMAE and MMAF, and readers also meet it in the Sacituzumab govitecan and Polatuzumab vedotin entries and the DESTINY-Breast03 and DESTINY-Breast04 papers.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Ogitani et al., Bystander killing effect of DS-8201a, a HER2-targeting antibody-drug conjugate (Cancer Science 2016)","url":"https://doi.org/10.1111/cas.12966"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ogitani-cancer-sci"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},"route":"/terms/bystander-effect/","neighbours":{"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"drug":[{"id":"polatuzumab-vedotin","kind":"drug","name":"Polatuzumab vedotin","route":"/drugs/polatuzumab-vedotin/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"paper":[{"id":"paper-ogitani-cancer-sci","kind":"paper","name":"Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity","route":"/key-papers/paper-ogitani-cancer-sci/"},{"id":"paper-destiny-breast03-nejm-2022","kind":"paper","name":"DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer","route":"/key-papers/paper-destiny-breast03-nejm-2022/"},{"id":"paper-destiny-breast04-nejm-2022","kind":"paper","name":"DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group","route":"/key-papers/paper-destiny-breast04-nejm-2022/"}],"idea":[{"id":"idea-bio1-tumour-on-chip-penetration","kind":"idea","name":"Tumour-on-a-chip with blood flow to test whether big drugs actually get in","route":"/ideas/idea-bio1-tumour-on-chip-penetration/"},{"id":"idea-bio1-antibody-degrader-conjugates","kind":"idea","name":"Use antibodies to deliver protein-destroying drugs into the right cells","route":"/ideas/idea-bio1-antibody-degrader-conjugates/"}],"term":[{"id":"cl2a","kind":"term","name":"CL2A","route":"/terms/cl2a/"},{"id":"dm1","kind":"term","name":"DM1","route":"/terms/dm1/"},{"id":"dm4","kind":"term","name":"DM4","route":"/terms/dm4/"},{"id":"dxd","kind":"term","name":"DXd","route":"/terms/dxd/"},{"id":"mc-vc-pabc","kind":"term","name":"mc-Val-Cit-PABC","route":"/terms/mc-vc-pabc/"},{"id":"mmae","kind":"term","name":"MMAE","route":"/terms/mmae/"},{"id":"mmaf","kind":"term","name":"MMAF","route":"/terms/mmaf/"},{"id":"topoisomerase-i-payloads","kind":"term","name":"Topoisomerase-I inhibitor payloads","route":"/terms/topoisomerase-i-payloads/"},{"id":"tubulin-inhibitor-payloads","kind":"term","name":"Tubulin inhibitor payloads","route":"/terms/tubulin-inhibitor-payloads/"}],"pathway":[{"id":"drug-efflux-pumps","kind":"pathway","name":"Drug efflux pumps (ABC transporters)","route":"/pathways/drug-efflux-pumps/"}]}}