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In Vitro and In Vivo Efficacy of a Stroma-Targeted, Tumor Microenvironment Responsive Oncolytic Adenovirus in Different Preclinical Models of Cancer.
Alfano, Ana; Cafferata, Eduardo G A; Gangemi, Mariela; Nicola Candia, Alejandro; Malnero, Cristian M; Bermudez, Ismael; Lopez, Mauricio Vargas; Ríos, Gregorio David; Rotondaro, Cecilia; Cuneo, Nicasio; Curiel, David T; Podhajcer, Osvaldo L; Lopez, Maria Veronica.
Afiliação
  • Alfano A; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Cafferata EGA; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Gangemi M; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Nicola Candia A; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Malnero CM; Facultad de Ingeniería, Universidad Argentina de la Empresa, Lima 775, Ciudad Autónoma de Buenos Aires C1073AAO, Argentina.
  • Bermudez I; Facultad de Ingeniería, Universidad Argentina de la Empresa, Lima 775, Ciudad Autónoma de Buenos Aires C1073AAO, Argentina.
  • Lopez MV; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Ríos GD; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Rotondaro C; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Cuneo N; Servicio de Ginecología, Departamento de Cirugía, Hospital Municipal de Oncología Maria Curie, Avenida Patricias Argentinas 750, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Curiel DT; Division of Cancer Biology, Department of Radiation Oncology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
  • Podhajcer OL; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
  • Lopez MV; Laboratory of Molecular and Cellular Therapy, Instituto Leloir, IIBBA-CONICET, Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
Int J Mol Sci ; 24(12)2023 Jun 10.
Article em En | MEDLINE | ID: mdl-37373140
More than one million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at a late stage, either because a lack of symptoms, such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries, such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV), whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer, uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404), a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Neoplasias do Colo do Útero / Infecções por Adenoviridae / Vírus Oncolíticos / Terapia Viral Oncolítica Limite: Animals / Female / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Argentina

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Neoplasias do Colo do Útero / Infecções por Adenoviridae / Vírus Oncolíticos / Terapia Viral Oncolítica Limite: Animals / Female / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Argentina