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AAV9-shCD155 (also written as AAV9_shCD155) is a preclinical recombinant gene therapy construct designed to knock down the expression of CD155 (poliovirus receptor, PVR) via RNA interference. It consists of an adeno-associated virus serotype 9 (AAV9) vector delivering a short hairpin RNA (shRNA) sequence targeting human CD155. CD155 is an immune-checkpoint ligand that binds to TIGIT on T cells and natural killer (NK) cells, promoting immune evasion. In non-small cell lung cancer (NSCLC), CD155 also drives tumor cell-intrinsic glycolysis and resistance to anti-PD-1 therapy via the PI3K/AKT/HIF-1α signaling pathway. In preclinical models, intratumoral administration of AAV9-shCD155 has been shown to inhibit tumor growth and postoperative recurrence, and to act synergistically with anti-PD-1 therapies (such as pembrolizumab) to enhance immune cell infiltration and overcome treatment resistance.
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