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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4591-4601
Adenovirus Vector-Based Purging of Multiple Myeloma Cells
Gerrard Teoh,
Ling Chen,
Mitsuyoshi Urashima,
Yu-Tzu Tai,
Leo A. Celi,
Dongshu Chen,
Dharminder Chauhan,
Atsushi Ogata,
Robert W. Finberg,
Iain J. Webb,
Donald W. Kufe, and
Kenneth C. Anderson
From the Department of Adult Oncology, Dana-Farber Cancer Institute,
Boston, MA; and the Department of Haematology, Singapore General
Hospital, Singapore.
Adenoviruses are efficient gene delivery agents for a variety of
neoplasms. In the present study, we have investigated the use of
adenoviruses for the delivery of the thymidine kinase
(tk) gene into multiple myeloma (MM) cells. We first
demonstrated that MM cell lines and MM patient cells express both
adenovirus receptors as well as the DF3/MUC1 protein, thus providing a
rationale for using adenoviruses to selectively deliver genes under the
control of the DF3 promoter. By using an adenoviral construct
containing  -galactosidase (-gal) gene driven by
the DF3 promoter (Ad.DF3-gal), we demonstrate greater than
80% transduction efficiency in OCI-My5 and RPMI 8226 MM cell lines at
a multiplicity of infection of 1 to 100. Importantly, transduction with
the tk gene driven by the DF3 promoter (Ad.DF3-tk)
followed by treatment with 50 µmol/L ganciclovir (GCV) purged  6
log of contaminating OCI-My5 and RPMI 8226 MM cells within bone marrow
mononuclear cells. In contrast, normal human hematopoietic progenitor
cell number was unaffected under these conditions. Selectivity of
DF3/MUC1 promoter was further confirmed, because Ad.DF3-gal
or Ad.DF3-tk did not transduce MUC1-negative HeLa cervical
carcinoma cells. In addition, GCV treatment of
Ad.DF3-tk-transduced RPMI 8226 MM cells did not induce a
significant bystander effect. These findings demonstrate that transduction with Ad vectors using a tumor-selective promoter provides
a highly efficient and selective approach for the ex vivo purging of MM
cells.
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