Intratumoral immunostimulatory AdCD40L gene therapy in patients with advanced solid tumors.

Abstract

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.

• Authors: Sandra Irenaeus, Vivan Hellström, Jessica Wenthe, Johan Krause, Anders Sundin, Håkan Ahlström, Gunnar Tufveson, Thomas H Tötterman, Angelica Loskog, Gustav J Ullenhag
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 28 Issue 10-11 Pg. 1188-1197 (11 2021) ISSN: 1476-5500 [Electronic] England
• PMID: 33318679 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.

Topics

• Animals
• Female
• Genetic Therapy (methods)
• Humans
• Immunization (methods)
• Male
• Middle Aged
• Neoplasms (genetics, mortality)
• Survival Analysis