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Use of a lethally irradiated major histocompatibility complex nonrestricted
cytotoxic T-cell line for effective purging of marrows containing
lysis-sensitive or -resistant leukemic targets [see comments]
A Cesano, G Pierson, S Visonneau, AR Migliaccio and D Santoli
Wistar Institute, Philadelphia, PA 19104, USA.
Improved marrow purging protocols are needed in autologous bone marrow
transplantation (BMT) to achieve complete eradication of minimal residual
disease. This study investigates the potential of a human major
histocompatibility complex (MHC) nonrestricted killer T-cell line
(TALL-104) as a new marrow purging agent in a clinical setting. TALL- 104
cells can be irradiated without losing cytotoxic activity against tumor
targets in vitro. In vivo, the irradiated killers can be adoptively
transferred into immunodeficient and immunocompetent leukemia-bearing mice,
and reverse their disease even in advanced stages. The present study shows
that gamma-irradiated TALL-104 cells, cultured for 18 hours with marrows
from healthy donors, do not impair the viability and long-term growth of
committed and pluripotent hematopoietic progenitors. However, as determined
by polymerase chain reaction (PCR) and colony assays, TALL-104 cells could
completely purge marrows containing up to 50% lysis-susceptible
myelomonocytic leukemia cells (U937). When marrows were admixed with a
pre-B leukemia cell line (ALL-1), which is fairly resistant to TALL-104
cell lysis in longterm 51Cr-release assays but can be totally growth
inhibited by TALL-104 cells in proliferation assays, residual ALL-1 cells
were detectable by PCR after TALL-104 purging. However, importantly, these
PCR+ marrows were devoid of tumorigenic activity when transplanted into the
human hematopoietic microenvironment of human severe combined
immunodeficient (SCID) chimeras. These data indicate the strong potential
of the TALL- 104 cell line in future marrow purging strategies against
lysis- susceptible and -resistant leukemias.
Volume 87,
Issue 1,
pp. 393-403,
01/01/1996
Copyright © 1996 by The American Society of Hematology
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