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H-1 Parvovirus-Induced Oncolysis and Tumor Microenvironment Immune Modulation in a Novel Heterotypic Spheroid Model of Cutaneous T-Cell Lymphoma
by
, and
Assia Angelova
1,*
,
Milena Barf
1,
Alexandra Just
1,
Barbara Leuchs
2,
Jean Rommelaere
1 and
Guy Ungerechts
1,3 1
Clinical Cooperation Unit Virotherapy, Infection, Inflammation and Cancer Program, German Cancer Research Center, 69120 Heidelberg, Germany
2
Biopharmaceutical Production and Development Unit, German Cancer Research Center, 69120 Heidelberg, Germany
3
Department of Medical Oncology, National Center for Tumor Diseases Heidelberg and Heidelberg University Hospital, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(15), 2711; https://doi.org/10.3390/cancers16152711
Submission received: 25 June 2024
/
Revised: 23 July 2024
/
Accepted: 26 July 2024
/
Published: 30 July 2024
(This article belongs to the Special Issue Oncolytic Viruses as an Emerging Aspect of Immune Oncology)
Simple Summary
Cutaneous T-cell lymphoma (CTCL) is a rare type of T-lymphocyte malignancy strongly calling for novel therapies. Virotherapy by means of oncolytic viruses that are able to kill cancer cells, while sparing healthy cells, is a promising innovative form of anticancer immunotherapy. The aim of this study was to investigate the potential of an oncolytic parvovirus, H-1PV, to induce selective killing (oncolysis) of CTCL cells and suppress the growth of CTCL spheroids. We demonstrated that H-1PV treatment led to oncolysis in tumor, but not in control normal cells. Oncolysis ensued despite pro-survival protein overexpression and was associated with the release of danger-signaling molecules. In heterotypic CTCL spheroids, H-1PV induced spheroid growth suppression and, upon co-culturing with peripheral blood mononuclear cells, spheroid infiltration with immune cells. In summary, we gathered the first preclinical data showing that H-1PV holds significant potential to become a novel viroimmunotherapeutic agent against CTCL.
Abstract
The rat protoparvovirus H-1 (H-1PV) is an oncolytic virus known for its anticancer properties in laboratory models of various human tumors, including non-Hodgkin lymphomas (NHL) of B-cell origin. However, H-1PV therapeutic potential against hematological malignancies of T-cell origin remains underexplored. The aim of the present study was to conduct a pilot preclinical investigation of H-1PV-mediated oncolytic effects in cutaneous T-cell lymphoma (CTCL), a type of NHL that is urgently calling for innovative therapies. We demonstrated H-1PV productive infection and induction of oncolysis in both classically grown CTCL suspension cultures and in a novel, in vivo-relevant, heterotypic spheroid model, but not in healthy donor controls, including peripheral blood mononuclear cells (PBMCs). H-1PV-mediated oncolysis of CTCL cells was not prevented by Bcl-2 overexpression and was accompanied by increased extracellular ATP release. In CTCL spheroid co-cultures with PBMCs, increased spheroid infiltration with immune cells was detected upon co-culture treatment with the virus. In conclusion, our preclinical data show that H-1PV may hold significant potential as an ingenious viroimmunotherapeutic drug candidate against CTCL.
