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Immunological data from cancer patients treated with Ad5/3-E2F-Δ24-GMCSF suggests utility for tumor immunotherapy.
- Source :
-
Oncotarget [Oncotarget] 2015 Feb 28; Vol. 6 (6), pp. 4467-81. - Publication Year :
- 2015
-
Abstract
- Oncolytic viruses that selectively replicate in tumor cells can be used for treatment of cancer. Accumulating data suggests that virus induced oncolysis can enhance anti-tumor immunity and break immune tolerance. To capitalize on the immunogenic nature of oncolysis, we generated a quadruple modified oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF). Ad5/3-E2F-Δ24-GMCSF (CGTG-602) was engineered to contain a tumor specific E2F1 promoter driving an E1 gene deleted at the retinoblastoma protein binding site ("Δ24"). The fiber features a knob from serotype 3 for enhanced gene delivery to tumor cells. The virus was tested preclinically in vitro and in vivo and then 13 patients with solid tumors refractory to standard therapies were treated. Treatments were well tolerated and frequent tumor- and adenovirus-specific T-cell immune responses were seen. Overall, with regard to tumor marker or radiological responses, signs of antitumor efficacy were seen in 9/12 evaluable patients (75%). The radiological disease control rate with positron emission tomography was 83% while the response rate (including minor responses) was 50%. Tumor biopsies indicated accumulation of immunological cells, especially T-cells, to tumors after treatment. RNA expression analyses of tumors indicated immunological activation and metabolic changes secondary to virus replication.
- Subjects :
- Adult
Aged
Animals
Antibodies, Neutralizing blood
Antibodies, Viral blood
Cricetinae
E2F1 Transcription Factor genetics
Female
Humans
Male
Mesocricetus
Middle Aged
Oncolytic Viruses
Promoter Regions, Genetic
Xenograft Model Antitumor Assays
Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage
Immunotherapy methods
Neoplasms therapy
Oncolytic Virotherapy methods
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25714011
- Full Text :
- https://doi.org/10.18632/oncotarget.2901