{"entity":{"id":"immune-stimulating-adc","kind":"technology","name":"Immune-stimulating antibody conjugate (ISAC)","aka":[],"tldr":"An immune-stimulating antibody conjugate (ISAC) is an ADC whose payload wakes up the immune system inside the tumour rather than poisoning the cell.","summary":"An immune-stimulating antibody conjugate delivers an innate immune agonist, rather than a cytotoxic, to tumour-resident myeloid cells, aiming to convert immunologically cold tumours into hot ones. TLR7/8 agonist conjugates (Bolt's BDC-1001 against HER2; Silverback) and STING agonist conjugates (Mersana XMT-2056, Takeda TAK-500) are the leading examples. In principle the approach could produce durable immune memory and combine naturally with checkpoint inhibitors. Early results have been modest, with weak single-agent activity so far; dose-limiting systemic cytokine release and the need for antigen-presenting-cell engagement are the challenges. The simple version is an ADC whose payload wakes up the immune system inside the tumour, an idea still waiting for convincing clinical proof.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"Ackerman et al., Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumour immunity (Nature Cancer 2020)","url":"https://doi.org/10.1038/s43018-020-00136-x"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["adcs","immunotherapy"],"technologies":["adc","sting-agonist"],"targets":[],"drugs":[],"companies":["nbe-therapeutics","tallac-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ackerman-nat-cancer"],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibody-targeted delivery of innate immune agonists to tumour-resident myeloid cells.","generation":"4th (next-gen)","strengths":["Durable immune memory in principle","Combinable with checkpoint inhibitors"],"limitations":["Weak single-agent activity so far"]},"route":"/technologies/immune-stimulating-adc/","neighbours":{"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"sting-agonist","kind":"technology","name":"STING & innate immune agonists","route":"/technologies/sting-agonist/"}],"company":[{"id":"mersana","kind":"company","name":"Mersana Therapeutics","route":"/companies/mersana/"},{"id":"nbe-therapeutics","kind":"company","name":"NBE-Therapeutics","route":"/companies/nbe-therapeutics/"},{"id":"tallac-therapeutics","kind":"company","name":"Tallac Therapeutics","route":"/companies/tallac-therapeutics/"}],"paper":[{"id":"paper-ackerman-nat-cancer","kind":"paper","name":"Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity","route":"/key-papers/paper-ackerman-nat-cancer/"}],"pathway":[{"id":"cgas-sting","kind":"pathway","name":"cGAS-STING innate sensing","route":"/pathways/cgas-sting/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"}]}}