Oncolytic adenovirus MEM-288 encoding membrane-stable CD40L and IFNβ induces an anti-tumor immune response in high grade serous ovarian cancer.

Publisher: Elsevier Country of Publication: United States NLM ID: 100886622 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5586 (Electronic) Linking ISSN: 14765586 NLM ISO Abbreviation: Neoplasia Subsets: MEDLINE

Publication: 2014- : [Amsterdam] : Elsevier
Original Publication: New York, NY : Stockton Press, c1999-

Ovarian Neoplasms*/therapy ; Ovarian Neoplasms*/immunology ; Ovarian Neoplasms*/pathology ; Ovarian Neoplasms*/genetics ; Adenoviridae*/genetics ; Oncolytic Viruses*/genetics ; Oncolytic Viruses*/immunology ; Interferon-beta*/genetics ; Interferon-beta*/metabolism ; Oncolytic Virotherapy*/methods ; Tumor Microenvironment*/immunology ; CD40 Ligand*/genetics ; CD40 Ligand*/metabolism ; Cystadenocarcinoma, Serous*/therapy ; Cystadenocarcinoma, Serous*/immunology ; Cystadenocarcinoma, Serous*/pathology ; Cystadenocarcinoma, Serous*/genetics ; Xenograft Model Antitumor Assays*; Female ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Genetic Vectors/genetics ; Genetic Vectors/administration & dosage ; Disease Models, Animal ; Neoplasm Grading ; Immunotherapy/methods

Single agent immune checkpoint inhibitors have been ineffective for patients with advanced stage and recurrent high grade serous ovarian cancer (HGSOC). Using pre-clinical models of HGSOC, we evaluated the anti-tumor and immune stimulatory effects of an oncolytic adenovirus, MEM-288. This conditionally replicative virus encodes a modified membrane stable CD40L and IFNβ. We demonstrated this virus successfully infects HGSOC cell lines and primary human ascites samples in vitro. We evaluated the anti-tumor and immunostimulatory activity in vivo in immune competent mouse models. Intraperitoneal delivery of MEM-288 decreased ascites and solid tumor burden compared to controls, and treatment generated a systemic anti-tumor immune response. The tumor microenvironment had a higher proportion of anti-tumor macrophages and decreased markers of angiogenesis. MEM-288 is a promising immunotherapy agent in HGSOC, with further pre-clinical studies required to understand the mechanism of action in the peritoneal microenvironment and clinical activity in combination with other therapies.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark Cantwell is an employee, stock owner of Memgen, Inc and has a patent on MEM-288.
(Copyright © 2024. Published by Elsevier Inc.)

K12 HD103083 United States HD NICHD NIH HHS; T32 CA211056 United States CA NCI NIH HHS

Keywords: Ascites; ELISA; ELISPOT; Immunotherapy; Intraperitoneal; Microenvironment; Oncolytic virus; Ovarian cancer

77238-31-4 (Interferon-beta)
147205-72-9 (CD40 Ligand)

Date Created: 20240914 Date Completed: 20241010 Latest Revision: 20241210

20241210

PMC11417341

10.1016/j.neo.2024.101056

39276533