The Oncolytic Virotherapy Era in Cancer Management: Prospects of Applying H-1 Parvovirus to Treat Blood and Solid Cancers

Abstract

Non-Hodgkin lymphoma (NHL) and leukemia are among the most common cancers worldwide. While the treatment of NHL/leukemia of B-cell origin has much progressed with the introduction of targeted therapies, few treatment standards have been established for T-NHL/leukemia. As presentation in both B- and T-NHL/leukemia patients is often aggressive and as prognosis for relapsed disease is especially dismal, this cancer entity poses major challenges and requires innovative therapeutic approaches. In clinical trials, oncolytic viruses (OVs) have been used against refractory multiple myeloma (MM). In preclinical settings, a number of OVs have demonstrated a remarkable ability to suppress various types of hematological cancers. Most studies dealing with this approach have used MM or B- or myeloid-cell-derived malignancies as models. Only a few describe susceptibility of T-cell lymphoma/leukemia to OV infection and killing. The rat H-1 parvovirus (H-1PV) is an OV with considerable promise as a novel therapeutic agent against both solid tumors (pancreatic cancer and glioblastoma) and hematological malignancies. The present perspective article builds on previous reports of H-1PV-driven regression of Burkitt’s lymphoma xenografts and on unpublished observations demonstrating effective killing by H-1PV of cells from CHOP-resistant diffuse large B-cell lymphoma, cutaneous T-cell lymphoma, and T-cell acute lymphoblastic leukemia. On the basis of these studies, H-1PV is proposed for use as an adjuvant to (chemo)therapeutic regimens. Furthermore, in the light of a recently completed first parvovirus clinical trial in glioblastoma patients, the advantages of H-1PV for systemic application are discussed.

Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

“…Oncolytic viruses were recently developed for the treatment of blood and solid cancers. 2 They can infect and kill malignant cells while sparing their normal counterparts. 5 So far, there has been no study to report that oVV was applied to treat AML, although oncolytic virus therapy has been used for the treatment of other cancers.…”

“…The tumor growth was measured every 3 days and the volume (V, mm 3 was computed using the formula: V=1/2 × length × width) was determined. 2 When the volume of tumors approximately grew up to 200 mm, the mice were injected with PBS, cytarabine, oVV, oVV-ING4 or cytarabine, and oVV-ING4. After 1 week, the tumors of two mice from each group were collected and digested with the help of enzymes into cell suspensions, and then subjected to flow cytometry with Annexin V-FITC/PI double staining.…”

Development of oncolytic virotherapy: from genetic modification to combination therapy

“…H-1PV nonstructural protein 1 (NS1) is important for promoting tumor cell death. Preclinical studies suggested that H-1PV can effectively kill various tumor cells [56], including pancreatic ductal adenocarcinoma cells and glioma cells [61]. In particular, ParvOryx (wild-type H-1PV) showed an excellent safety profile in phase I/IIa clinical trials [8].…”

Prospects for combined use of oncolytic viruses and CAR T-cells

“…With the FDA’s recent approval of tisagenlecleucel for children and young adults with ALL, it is intriguing to consider whether CAR and OV synergism could be evaluated in haematological malignancy, thus potentially accelerating proof of principle. Certainly, a number of OVs (such as parvovirus and NDV) have been evaluated in preclinical models of leukaemia, lymphoma and myeloma [ 220 , 221 ]. The local induction of innate immunity following OV infection coupled with the potential to enhance CAR T-cell homing and effector function by inserting specific transgenes into the OV genome may be expected to yield improved results with CD19-directed CAR T-cells.…”