CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma.

Autor:	Hanauer JDS; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany., Rengstl B; Dr. Senckenberg Institute of Pathology, Goethe-University Frankfurt, Frankfurt am Main, Germany.; Current address: BioNTech Cell and Gene Therapies GmbH, 55131 Mainz, Germany., Kleinlützum D; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany., Reul J; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany., Pfeiffer A; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany., Friedel T; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany., Schneider IC; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany., Newrzela S; Dr. Senckenberg Institute of Pathology, Goethe-University Frankfurt, Frankfurt am Main, Germany.; Current address: BioNTech Cell and Gene Therapies GmbH, 55131 Mainz, Germany., Hansmann ML; Dr. Senckenberg Institute of Pathology, Goethe-University Frankfurt, Frankfurt am Main, Germany., Buchholz CJ; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany., Muik A; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.; Current address: BioNTech RNA Pharmaceuticals GmbH, 55131 Mainz, Germany.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 Jan 12; Vol. 9 (16), pp. 12971-12981. Date of Electronic Publication: 2018 Jan 12 (Print Publication: 2018).
DOI:	10.18632/oncotarget.24191
Abstrakt:	Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While most patients with early stage cHL can be cured by standard therapy, treatment options for relapsed or refractory cHL are still not sufficient, although immunotherapy-based approaches for the treatment of cHL patients have gained ground in the last decade. Here, we suggest a novel therapeutic concept based on oncolytic viruses selectively destroying the CD30 + -positive cHL tumor cells. Relying on a recently described CD30-specific scFv we have generated CD30-targeted measles virus (MV-CD30) and vesicular stomatitis virus (VSV-CD30). For VSV-CD30 the VSV glycoprotein G reading frame was replaced by those of the CD30-targeted MV glycoproteins. Both viruses were found to be highly selective for CD30-positive cells as demonstrated by infection of co-cultures of target and non-target cells as well as through blocking infection by soluble CD30. Notably, VSV-CD30 yielded much higher titers than MV-CD30 and resulted in a more rapid and efficient killing of cultivated cHL-derived cell lines. Mouse tumor models revealed that intratumorally, as well as systemically injected VSV-CD30, infected cHL xenografts and significantly slowed down tumor growth resulting in a substantially prolonged survival of tumor-bearing mice. Taken together, the data support further preclinical testing of VSV-CD30 as novel therapeutic agent for the treatment of cHL and other CD30 + -positive malignancies. Competing Interests: CONFLICTS OF INTEREST None.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu