AdCD40L is a replication-deficient virus carrying the gene for CD40 ligand which has previously been evaluated in patients with urothelial cancer and malignant melanoma. Herein, we present the results of repeated intratumoral injections of AdCD40L in seven patients with metastatic solid cancer. One patient who developed urothelial cancer derived from a renal transplant was treated with repeated injections of AdCD40L alone. The remaining patients suffered from cholangiocarcinoma, kidney, breast, rectal, or ovarian cancer and received AdCD40L repeatedly (4x) in combination with cyclophosphamide. The treatment was safe and generally well-tolerated. Two patients had clinical benefit of the treatment and one of them was accepted for re-treatment. Circulating proinflammatory cytokines were commonly increased after treatment, but save for TNFα, significances were not reached which could be due to the low number of patients. Similar to earlier findings in AdCD40L-treated melanoma patients, IL8 plasma levels were high in the present study. In conclusion, gene therapy by repeated intratumoral AdCD40L injections alone, or in combination with cyclophosphamide, is feasible and safe in patients with solid cancers. The potential of intratumoral CD40L gene transfer as treatment of cancer was illustrated by the clinical improvement in two out of seven patients.

AdCD40L 是一种复制缺陷型病毒，携带 CD40 配体基因，此前已在患有尿路上皮癌和恶性黑色素瘤的患者中进行了评估。在此，我们展示了在 7 名转移性实体癌患者中反复瘤内注射 AdCD40L 的结果。一名因肾移植而患上尿路上皮癌的患者接受了反复单独注射 AdCD40L 的治疗。其余患者患有胆管癌、肾癌、乳腺癌、直肠癌或卵巢癌，并反复接受 AdCD40L (4x) 与环磷酰胺联合治疗。治疗是安全的并且通常耐受性良好。两名患者从治疗中获得临床益处，其中一名患者接受了再治疗。治疗后循环促炎细胞因子通常增加，但除了 TNFα，没有达到显着性，这可能是由于患者数量少。与 AdCD40L 治疗的黑色素瘤患者的早期发现相似，本研究中 IL8 血浆水平较高。总之，通过单独重复瘤内注射AdCD40L或与环磷酰胺联合进行基因治疗，对实体癌患者是可行且安全的。7 名患者中有 2 名的临床改善说明了肿瘤内 CD40L 基因转移作为癌症治疗的潜力。在实体癌患者中是可行和安全的。7 名患者中有 2 名的临床改善说明了肿瘤内 CD40L 基因转移作为癌症治疗的潜力。在实体癌患者中是可行和安全的。7 名患者中有 2 名的临床改善说明了肿瘤内 CD40L 基因转移作为癌症治疗的潜力。