SPARC: A Multipayload ADC Architecture for Programmable Drug Combinations.

ABSTRACT: Drug combination is a cornerstone of modern medicine, particularly in oncology. However, drug combinations often fail due to poor disease site tropism and additive toxicities of composite drugs. Among targeted drug delivery systems for reducing toxicity, the antibody-drug conjugate (ADC) is effective for single cytotoxic payload delivery. Multipayload ADC for combination therapy is mostly limited to two chemotherapeutics at fixed ratios, hampered by a lack of payload combination synergy/toxicity knowledge and complex antibody engineering and linker chemistries. Here we design synergistic payload-antibody ratiometric conjugate (SPARC) based on an elucidation of payload ratio-dependent pharmacology and toxicology of drug combinations delivered by a previously described clinical-stage T1000-A

SUBMITTER: Sun W 

PROVIDER: S-EPMC12532090 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature