H-1 Parvovirus-Induced Oncolysis and Tumor Microenvironment Immune Modulation in a Novel Heterotypic Spheroid Model of Cutaneous T-Cell Lymphoma

• Published in: Cancers Vol. 16; no. 15; p. 2711
• Main Authors: Angelova, Assia, Barf, Milena, Just, Alexandra, Leuchs, Barbara, Rommelaere, Jean, Ungerechts, Guy
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2024
• Subjects: Antibiotics; Bcl-2 protein; Cancer research; Cell culture; Cell growth; Drug development; Fibroblasts; Health aspects; Immunomodulation; Immunotherapy; Infiltration; Leukocytes (mononuclear); Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Malignancy; Measles; Medical research; Metastases; Non-Hodgkin's lymphomas; Oncolysis; Parvoviruses; Peripheral blood mononuclear cells; Proteins; Research centers; Spheroids; T cells; T-cell lymphoma; Tumor microenvironment; Tumors; Viruses; Germany; oncolytic H-1 parvovirus; heterotypic CTCL spheroid; cutaneous T-cell lymphoma (CTCL); virotherapy
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16152711

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.