Department of Immunology, Genetics and Pathology, Science of Life Laboratory, Uppsala University, Dag Hammarskjolds vag 20, 751 85, Uppsala, Sweden.
Department of Oncology, Uppsala University Hospital, 751 85, Uppsala, Sweden.
Cancer Gene Ther. 2021 Nov;28(10-11):1188-1197. doi: 10.1038/s41417-020-00271-8. Epub 2020 Dec 14.
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，此前已在膀胱癌和恶性黑色素瘤患者中进行了评估。在此，我们报告了 7 例转移性实体瘤患者重复瘤内注射 AdCD40L 的结果。1 例由肾移植引起的尿路上皮癌患者单独接受了重复 AdCD40L 注射治疗。其余患者患有胆管癌、肾癌、乳腺癌、直肠癌或卵巢癌，接受了重复（4 次）瘤内注射 AdCD40L 联合环磷酰胺治疗。治疗安全且通常耐受良好。2 例患者有治疗的临床获益，其中 1 例接受了再治疗。治疗后循环中促炎细胞因子普遍增加，但除 TNFα 外，均未达到统计学意义，这可能是由于患者数量较少。与之前在接受 AdCD40L 治疗的黑色素瘤患者中观察到的结果相似，本研究中 IL8 血浆水平较高。总之，单独重复瘤内注射 AdCD40L 或联合环磷酰胺进行基因治疗在实体瘤患者中是可行且安全的。7 例患者中有 2 例的临床改善表明瘤内 CD40L 基因转移作为癌症治疗的潜力。
