# Bystander effect (ADC)

Source: https://onco.cc/terms/bystander-effect/  
OnCo record `bystander-effect` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-04

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Antibody-drug_conjugate
- Ogitani et al., Bystander killing effect of DS-8201a, a HER2-targeting antibody-drug conjugate (Cancer Science 2016): https://doi.org/10.1111/cas.12966

## Connected records

- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- drugs: [Polatuzumab vedotin](https://onco.cc/drugs/polatuzumab-vedotin/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- key papers: [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](https://onco.cc/key-papers/paper-ogitani-cancer-sci/), [DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer](https://onco.cc/key-papers/paper-destiny-breast03-nejm-2022/), [DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group](https://onco.cc/key-papers/paper-destiny-breast04-nejm-2022/)
- ideas: [Tumour-on-a-chip with blood flow to test whether big drugs actually get in](https://onco.cc/ideas/idea-bio1-tumour-on-chip-penetration/), [Use antibodies to deliver protein-destroying drugs into the right cells](https://onco.cc/ideas/idea-bio1-antibody-degrader-conjugates/)
- terms: [CL2A](https://onco.cc/terms/cl2a/), [DM1](https://onco.cc/terms/dm1/), [DM4](https://onco.cc/terms/dm4/), [DXd](https://onco.cc/terms/dxd/), [mc-Val-Cit-PABC](https://onco.cc/terms/mc-vc-pabc/), [MMAE](https://onco.cc/terms/mmae/), [MMAF](https://onco.cc/terms/mmaf/), [Topoisomerase-I inhibitor payloads](https://onco.cc/terms/topoisomerase-i-payloads/), [Tubulin inhibitor payloads](https://onco.cc/terms/tubulin-inhibitor-payloads/)
- pathways: [Drug efflux pumps (ABC transporters)](https://onco.cc/pathways/drug-efflux-pumps/)

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