Immune-stimulating antibody conjugate (ISAC)

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.