{"entity":{"id":"paper-ackerman-nat-cancer","kind":"paper","name":"Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 35121890 and published in Nature Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Innate pattern recognition receptor agonists, including Toll-like receptors (TLRs), alter the tumor microenvironment and prime adaptive antitumor immunity. However, TLR agonists present toxicities associated with widespread immune activation after systemic administration. To design a TLR-based therapeutic suitable for systemic delivery and capable of safely eliciting tumor-targeted responses, we developed immune-stimulating antibody conjugates (ISACs) comprising a TLR7/8 dual agonist conjugated to tumor-targeting antibodies. Systemically administered human epidermal growth factor receptor 2 (HER2)-targeted ISACs were well tolerated and triggered a localized immune response in the tumor microenvironment that resulted in tumor clearance and immunological memory. Mechanistically, ISACs required tumor antigen recognition, Fcγ-receptor-dependent phagocytosis and TLR-mediated activation to drive tumor killing by myeloid cells and subsequent T-cell-mediated antitumor immunity. ISAC-mediated immunological memory was not limited to the HER2 ISAC target antigen since ISAC-treated mice were protected from rechallenge with the HER2 - parental tumor. These results provide a strong rationale for the clinical development of ISACs.\n\nIndexed on Europe PMC as PubMed record 35121890 (DOI 10.1038/s43018-020-00136-x). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Cancer 2021","url":"https://doi.org/10.1038/s43018-020-00136-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35121890/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35121890"}],"tags":["europepmc-ingest"],"related":["immune-stimulating-adc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Cancer","year":2021,"doi":"10.1038/s43018-020-00136-x","pmid":"35121890","authors":"Ackerman SE, Pearson CI, Gregorio JD, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-ackerman-nat-cancer/","neighbours":{"technology":[{"id":"immune-stimulating-adc","kind":"technology","name":"Immune-stimulating antibody conjugate (ISAC)","route":"/technologies/immune-stimulating-adc/"}],"journal":[{"id":"nature-cancer","kind":"journal","name":"Nature Cancer","route":"/journals/nature-cancer/"}]}}