A Novel HSV-1 Virus, JS1/34.5−/47−, Purges Contaminating Breast Cancer Cells From Bone Marrow

Hu, Juguang; Booth, Matthew J.; Tripuraneni, Gopichand; Davies, Derek; Zaidi, S A A; Bella, Manuela Tamburo De; Slade, Martin J.; Marley, Stephen B.; Gordon, Myrtle Y.; Coffin, Robert S.; Coombes, R. Charles; Kamalati, Tahereh

doi:10.1158/1078-0432.ccr-06-1228

Cited by 14 publications

(7 citation statements)

References 42 publications

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“…A recombinant HSV-1 vector (JS1/34.5-/47-) with deletions of the ICP34.5 and ICP47 genes, permitting tumor-selective replication and enhanced antigen presentation in HSV-infected cells, was reported to successfully infect breast cancer cells, without affecting normal bone marrow cells in vitro (22). Similar results were found using another recombinant HSV-1 (HSV-1/G207) in an in vitro infection model (23).…”

Section: Virus-mediated Oncolysis and Cancer Therapymentioning

confidence: 99%

Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with Myxoma virus

Rahman

Madlambayan

Cogle

et al. 2010

Cytokine & Growth Factor Reviews

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High-dose chemotherapy and radiation followed by autologous blood and marrow transplantation (ABMT) has been extensively used for the treatment of certain cancers that are refractory to standard therapeutic regimes. However, a major challenge with ABMT for patients with hematologic malignancies is disease relapse, mainly due to either contamination with cancerous hematopoietic stem and progenitor cells (HSPCs) within the autograft or the persistence of residual therapy-resistant disease niches within the patient. Oncolytic viruses represent a promising therapeutic approach to prevent cancer relapse by eliminating tumor-initiating cells that contaminate the autograft. Here we summarize an ex vivo "purging" strategy with oncolytic myxoma virus (MYXV) to remove cancerinitiating cells from patient autografts prior to transplantation. MYXV, a novel oncolytic poxvirus with potent anti-cancer properties in a variety of in vivo tumor models, can specifically eliminate cancerous stem and progenitor cells from samples obtained from acute myelogenous leukemia (AML) patients, while sparing normal CD34+ hematopoietic stem and progenitor cells capable of rescuing hematopoiesis following high dose conditioning. We propose that a broader subset of patients with intractable hematologic malignancies who have failed standard therapy could become eligible for ABMT when the treatment schema is coupled with ex vivo oncolytic therapy.

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Section: Virus-mediated Oncolysis and Cancer Therapymentioning

confidence: 99%

Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with Myxoma virus

Rahman

Madlambayan

Cogle

et al. 2010

Cytokine & Growth Factor Reviews

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“…Several genetic modifications of HSV-1 have been introduced to create strains with reduced viral pathogenicity and improved oncolytic abilities. 59 Hu et al 60 showed that the JS-1 strain could selectively kill MDA-MB-231 breast cancer cells when mixed with healthy bone marrow. Additionally, bone marrow samples from breast cancer patients were effectively purged with up to a 95% reduction of contaminating cancer cells, as quantified by cytokeratin-19 expression.…”

Section: Agents That Have Been Used In Preclinical Models Of Graft Pumentioning

confidence: 99%

The ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications

Tsang

Atkins

2015

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Hematological malignancies are treated with intensive high-dose chemotherapy, with or without radiation. This is followed by hematopoietic stem cell (HSC) transplantation (HSCT) to rescue or reconstitute hematopoiesis damaged by the anticancer therapy. Autologous HSC grafts may contain cancer cells and purging could further improve treatment outcomes. Similarly, allogeneic HSCT may be improved by selectively purging alloreactive effector cells from the graft rather than wholesale immune cell depletion. Viral agents that selectively replicate in specific cell populations are being studied in experimental models of cancer and immunological diseases and have potential applications in the context of HSC graft engineering. This review describes preclinical studies involving oncolytic virus strains of adenovirus, herpes simplex virus type 1, myxoma virus, and reovirus as ex vivo purging agents for HSC grafts, as well as in vitro and in vivo experimental studies using oncolytic coxsackievirus, measles virus, parvovirus, vaccinia virus, and vesicular stomatitis virus to eradicate hematopoietic malignancies. Alternative ex vivo oncolytic virus strategies are also outlined that aim to reduce the risk of relapse following autologous HSCT and mitigate morbidity and mortality due to graft-versus-host disease in allogeneic HSCT.

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“…To test for the expression of UL3 from the 2.6-kb transcript, I performed an immunoblot of uninfected and infected RS cell lysates using rabbit polyclonal antiserum to a GST-UL3 fusion protein (7). RS cells were infected at an MOI of 10 with the following virus: HSV-1(F), R7211, CB8115, or CB8116.…”

Section: Ul3 Transcripts the Two 3ј Coterminal Ul3-specific Transcrimentioning

confidence: 99%

“…This UL3 truncation appears to be limited to HSVs derived from the recombinant virus backbone R3617 (e.g., G207, MGH1, 3616UB, and G47⌬) (13,14,18,27). In contrast, viruses derived from other HSV strains or lineages (e.g., R3659, HSV1716, and Oncovex GM-CSF ) are expected to express an intact UL3 protein (3,(5)(6)(7)33). Because the function of UL3 is unknown, it is unclear whether the expression of a truncated or intact UL3 protein is optimal for viruses and vectors used in clinical trials.…”

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confidence: 99%

The Herpes Simplex Virus Type 1 UL3 Transcript Starts within the UL3 Open Reading Frame and Encodes a 224-Amino-Acid Protein

Markovitz

2007

J Virol

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Several different herpes simplex viruses (HSVs) and vectors are being explored as therapeutic products for use in the treatment of cancer and neurological disorders. The viral strain and the combination of mutant viral genes that ultimately may serve as a safe and optimal backbone for such products are still being explored. The large genome size and complexity of the viral life cycle make such determinations difficult, because the significance of differences between proposed products is difficult to evaluate. For example, we previously reported that two lineages of ␥34.

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A Novel HSV-1 Virus, JS1/34.5−/47−, Purges Contaminating Breast Cancer Cells From Bone Marrow

Cited by 14 publications

References 42 publications

Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with Myxoma virus

Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with Myxoma virus

The ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications

The Herpes Simplex Virus Type 1 UL3 Transcript Starts within the UL3 Open Reading Frame and Encodes a 224-Amino-Acid Protein

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