A novel HSV-1 virus, JS1/34.5-/47-, purges contaminating breast cancer cells from bone marrow.
OBJECTIVE
Oncolytic herpes simplex virus type 1 (HSV-1) vectors show considerable promise as agents for cancer therapy. We have developed a novel recombinant HSV-1 virus (JS1/34.5-/47-) for purging of occult breast cancer cells from bone marrow of patients. Here, we evaluate the therapeutic efficacy of this oncolytic virus.


METHODS
Electron microscopy was used to determine whether human breast cancer and bone marrow cells are permissive for JS1/34.5-/47- infection. Subsequently, the biological effects of JS1/34.5-/47- infection on human breast cancer cells and bone marrow were established using cell proliferation and colony formation assays, and the efficiency of cell kill was evaluated. Finally, the efficiency of JS1/34.5-/47- purging of breast cancer cells was examined in cocultures of breast cancer cells with bone marrow as well as bone marrow samples from high-risk breast cancer patients.


RESULTS
We show effective killing of human breast cancer cell lines with the JS1/34.5-/47- virus. Furthermore, we show that treatment with JS1/34.5-/47- can significantly inhibit the growth of breast cancer cell lines without affecting cocultured mononuclear hematopoietic cells. Finally, we have found that the virus is effective in destroying disseminated tumors cells in bone marrow taken from breast cancer patients, without affecting the hematopoietic contents in these samples.


CONCLUSIONS
Collectively, our data show that the JS1/34.5-/47- virus can selectively target breast cancer cells while sparing hematopoietic cells, suggesting that JS1/34.5-/47- can be used to purge contaminating breast cancer cells from human bone marrow in the setting of autologous hematopoietic cell transplantation.
Hu
Jennifer C
JC
Department of Oncology, Cancer Cell Biology Section, Imperial College Faculty of Medicine, University College London, UK.
Booth
Matthew J
MJ
Tripuraneni
Gopichand
G
Davies
Derek
D
Zaidi
Syed A A
SA
Tamburo de Bella
Manuela
M
Slade
Martin J
MJ
Marley
Stephen B
SB
Gordon
Myrtle Y A
MY
Coffin
Robert S
RS
Coombes
R Charles
RC
Kamalati
Tahereh
T
D000230:Adenocarcinoma / Q000473:pathology* / Q000821:virology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000821:virology; D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism; D042361:Mammary Glands, Human / Q000473:pathology / Q000821:virology; D050130:Oncolytic Virotherapy / Q000009:adverse effects; D050504:Oncolytic Viruses / Q000502:physiology*
D014408:Biomarkers, Tumor; D053539:Keratin-19