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- Title
Human Monocytes Are Suitable Carriers for the Delivery of Oncolytic Herpes Simplex Virus Type 1 In Vitro and in a Chicken Embryo Chorioallantoic Membrane Model of Cancer.
- Authors
Reale, Alberto; Krutzke, Lea; Cadamuro, Massimiliano; Vitiello, Adriana; von Einem, Jens; Kochanek, Stefan; Palù, Giorgio; Parolin, Cristina; Calistri, Arianna
- Abstract
Oncolytic viruses (OVs) are promising therapeutics for tumors with a poor prognosis. An OV based on herpes simplex virus type 1 (oHSV-1), talimogene laherparepvec (T-VEC), has been recently approved by the Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the treatment of unresectable melanoma. T-VEC, like most OVs, is administered via intratumoral injection, underlining the unresolved problem of the systemic delivery of the oncolytic agent for the treatment of metastases and deep-seated tumors. To address this drawback, cells with a tropism for tumors can be loaded ex vivo with OVs and used as carriers for systemic oncolytic virotherapy. Here, we evaluated human monocytes as carrier cells for a prototype oHSV-1 with a similar genetic backbone as T-VEC. Many tumors specifically recruit monocytes from the bloodstream, and autologous monocytes can be obtained from peripheral blood. We demonstrate here that oHSV-1-loaded primary human monocytes migrated in vitro towards epithelial cancer cells of different origin. Moreover, human monocytic leukemia cells selectively delivered oHSV-1 to human head-and-neck xenograft tumors grown on the chorioallantoic membrane (CAM) of fertilized chicken eggs after intravascular injection. Thus, our work shows that monocytes are promising carriers for the delivery of oHSV-1s in vivo, deserving further investigation in animal models.
- Subjects
EUROPEAN Medicines Agency; HUMAN herpesvirus 1; UNITED States. Food &; Drug Administration; CHICKEN embryos; CHORIOALLANTOIS; MONOCYTES; ONCOLYTIC virotherapy
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 11, p9255
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24119255