A Phase 1 Trial of Oncolytic Adenovirus ICOVIR-5 Administered Intravenously to Cutaneous and Uveal Melanoma Patients.
Hum Gene Ther
; 30(3): 352-364, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30234393
Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase 1 trial in metastatic melanoma patients. The results in 12 patients treated with a single infusion of a dose up to 1 × 1013 viral particles show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Adenoviridae
/
Virus Oncolíticos
/
Viroterapia Oncolítica
/
Vectores Genéticos
/
Melanoma
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Estados Unidos