Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer.
Edmonston vaccine strains of measles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS in patients with taxol- and platinum-resistant ovarian cancer. MV-NIS was given intraperitoneally every 4 weeks for up to 6 cycles. Treatment was well tolerated and associated with promising median overall survival in these patients with heavily pretreated ovarian cancer; no dose-limiting toxicity was observed in 16 patients treated at high-dose levels (10(8)-10(9) TCID50), and their median overall survival of 26.5 months compared favorably with other contemporary series. MV receptor CD46 and nectin-4 expression was confirmed by immunohistochemistry in patient tumors. Sodium iodide symporter expression in patient tumors after treatment was confirmed in three patients by (123)I uptake on SPECT/CTs and was associated with long progression-free survival. Immune monitoring posttreatment showed an increase in effector T cells recognizing the tumor antigens IGFBP2 and FRα, indicating that MV-NIS treatment triggered cellular immunity against the patients' tumor and suggesting that an immune mechanism mediating the observed antitumor effect. Our findings support further clinical evaluation of MV-NIS as an effective immunovirotherapy.
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota. Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota. galanis.evanthia@mayo.edu.
Evanthia
E
Galanis
Department of Statistics, Mayo Clinic, Rochester, Minnesota.
Pamela J
PJ
Atherton
Department of Statistics, Mayo Clinic, Rochester, Minnesota.
Matthew J
MJ
Maurer
Department of Immunology, Mayo Clinic, Rochester, Minnesota. Vaccine and Gene Therapy Institute of Florida, Port Saint Lucie, Florida.
Keith L
KL
Knutson
Division of Gynecological Surgery, Mayo Clinic, Rochester, Minnesota.
Sean C
SC
Dowdy
Division of Gynecological Surgery, Mayo Clinic, Rochester, Minnesota.
William A
WA
Cliby
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Paul
P
Haluska
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Harry J
HJ
Long
Department of Statistics, Mayo Clinic, Rochester, Minnesota.
Ann
A
Oberg
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
Ileana
I
Aderca
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Matthew S
MS
Block
Division of Gynecological Surgery, Mayo Clinic, Rochester, Minnesota.
Jamie
J
Bakkum-Gamez
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
Mark J
MJ
Federspiel
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
Stephen J
SJ
Russell
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Kimberly R
KR
Kalli
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Gary
G
Keeney
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
Kah Whye
KW
Peng
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Lynn C
LC
Hartmann
D000818:Animals; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008875:Middle Aged; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D019076:Transgenes; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D027981:Symporters; D000099209:Sodium-Iodide Symporters