Conditional biologics in cancer immunotherapy: mechanisms, applications and clinical progress.

Conditional biologics engineered to activate in response to tumour-associated signals or within the tumour microenvironment are proposed to uncouple efficacy from toxicity in cancer immunotherapy.

• Why it matters: Immunotherapy’s broader use is constrained by refractory indications, immune-related toxicities, and acquired resistance, including cytokine release syndrome and on-target, off-tumour effects.
• What they did: This Review summarizes mechanisms and applications of conditional activation, focusing on strategies such as tumour microenvironment–responsive protein engineering and evaluating completed and ongoing clinical trials.
• The result: The approach is positioned to expand the therapeutic window by improving tumour accumulation, restricting activity to specific cell types, and minimizing off-target effects, while addressing remaining logistical and technical barriers.

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