AAV-RGD

AAV-RGD is an engineered adeno-associated virus (AAV) gene therapy candidate developed by Allife Medicine for the treatment of solid tumors. The vector features a capsid modified with an RGD (Arg-Gly-Asp) peptide to enhance transduction efficiency in cancer cells by targeting cell-surface integrins. To ensure safety and tumor specificity, the therapy employs a dual-promoter system using PEG3 and CEA promoters to drive the expression of a pyroptosis-inducing payload, the N-terminal fragment of Gasdermin D (GSDMD-N). This system utilizes a Cre-FLEX (Flip-Excision) mechanism, where Cre recombinase and a reverse-oriented GSDMD-N cassette are placed under separate tumor-specific promoters, confining pyroptosis induction to cells where both promoters are active. Preclinical studies in liver cancer models demonstrated significant tumor suppression, and an investigator-initiated trial (IIT) in a patient with lung cancer and bone metastasis showed a loss of activity in metastatic lesions.