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Oncolytic adenovirus MEM-288 encoding membrane-stable CD40L and IFNß induces an anti-tumor immune response in high grade serous ovarian cancer.
Peters, Pamela N; Whitaker, Regina S; Lim, Felicia; Russell, Shonagh; Bloom, Elizabeth A; Pollara, Justin; Strickland, Kyle C; Cantwell, Mark J; Beg, Amer; Berchuck, Andrew; Antonia, Scott; Previs, Rebecca A.
Afiliación
  • Peters PN; Duke University Department of Obstetrics and Gynecology. Electronic address: pamela.peters@duke.edu.
  • Whitaker RS; Duke University Department of Obstetrics and Gynecology.
  • Lim F; Duke University Department of Pharmacology and Cancer Biology.
  • Russell S; Duke University Department of Pharmacology and Cancer Biology.
  • Bloom EA; Duke University School of Medicine.
  • Pollara J; Duke University Department of Surgery.
  • Strickland KC; Duke University Department of Pathology; Labcorp Oncology, Durham, NC, USA.
  • Cantwell MJ; Memgen, Inc.
  • Beg A; Moffitt Cancer Center Department of Immunology.
  • Berchuck A; Duke University Department of Obstetrics and Gynecology.
  • Antonia S; Labcorp Oncology, Durham, NC, USA.
  • Previs RA; Duke University Department of Obstetrics and Gynecology; Labcorp Oncology, Durham, NC, USA.
Neoplasia ; 57: 101056, 2024 Sep 13.
Article en En | MEDLINE | ID: mdl-39276533
ABSTRACT
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 IFNß. 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos