Biological purging of breast cancer cell lines using a replication-competent oncolytic virus in human stem cell autografts.
Autologous hematological stem cell transplantation (ASCT) is used for the treatment of many hematological and several solid cancers. ASCT, however, has proven disappointing as a therapeutic strategy for breast cancer. Our group and others have previously shown that breast cancer micrometastases found in patients' apheresis products (APs) predict shorter progression-free and overall survival. The implications of this finding are twofold: (i) contaminating tumor cells (CTCs) in AP reflect a higher systemic disease burden and/or (ii) reinfused CTCs contribute to relapse/progressive disease. To date, purging strategies have been disappointing. We have previously demonstrated the oncolytic properties of reovirus in in vitro, in vivo and ex vivo systems. In the present study, we tested the hypothesis that reovirus purges CTCs in a breast cancer cell line purging model. Reovirus-infected human breast cancer cell lines (HTB 133, HTB 132, SKBR3 and MCF7) exhibited cell death within days. Admixtures of AP with cells from breast tumor cell lines, which were then exposed to reovirus, showed complete purging of CTCs (assessed via flow cytometry/tumor cell outgrowth analysis) without deleterious effect on CD34+ cells. Our results provide preclinical support for the ex vivo use of reovirus as a purging modality for breast cancer during ASCT.
Thirukkumaran
C M
CM
Department of Medicine, Tom Baker Cancer Centre, 1331 29th Street NW, Calgary, Alberta, Canada T2N 4N2.
Luider
J M
JM
Stewart
D A
DA
Alain
T
T
Russell
J A
JA
Auer
I A
IA
Forsyth
P
P
Morris
D G
DG
D018952:Antigens, CD34 / Q000096:biosynthesis; D001781:Blood Component Removal; D016465:Bone Marrow Purging / Q000379:methods*; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D018450:Disease Progression; D018572:Disease-Free Survival; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008715:Methionine / Q000737:chemistry; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014780:Viruses / Q000235:genetics*
D018952:Antigens, CD34; D008715:Methionine; D017493:Leukocyte Common Antigens