Comparison of anti-Tac and anti-transferrin receptor-conjugated liposomes
for specific drug delivery to adult T-cell leukemia
KM Hege, DL Daleke, TA Waldmann and KK Matthay
Department of Pediatrics, University of California, San Francisco 94143.
Adult T-cell leukemia (ATL) is a rapidly progressive and usually fatal
malignancy of mature T cells characterized by the expression of large
numbers of interleukin-2 (IL-2) receptors on the cell surface. Anti- Tac, a
monoclonal antibody directed against the IL-2 receptor, was conjugated to
liposomes and compared with anti-transferrin receptor (anti-TFR) conjugates
for specific binding, internalization, and intracellular drug delivery to
ATL cells. Two independent assays were used: a fluorimetric assay with
liposome encapsulated 1-hydroxypyrene- 3,6,8-trisulfonic acid, a
pH-sensitive fluorescent dye, and a growth inhibition assay using
methotrexate-gamma-aspartate, a liposome- dependent cytotoxic drug. MT-1
and HUT-102 cell lines derived from patients with ATL were compared with
Molt-4, a leukemia cell line that does not express IL-2 receptors in an
uninduced state. Fluorimetric studies showed specific binding and
internalization of anti-Tac- conjugated liposomes by HUT-102 and MT-1 but
not by the Tac-negative cell line Molt-4, demonstrating the lack of
nonspecific or Fc receptor- mediated uptake. Anti-TFR-conjugated liposomes
were effectively bound and internalized by all three cell lines and
consistently showed the highest degree of cellular liposome uptake.
Drug-containing liposomes conjugated to anti-Tac were more than tenfold
more effective in causing growth inhibition of ATL cells than the
nonspecific control conjugates. Anti-Tac conjugates caused minimal growth
inhibition of Molt-4 cells over the concentration range effective against
the ATL cells. Anti-TFR- coupled liposomes gave better growth inhibition of
HUT-102 and MT-1 cells (40- to 60-fold) than anti-Tac conjugates. Both
anti-Tac-directed and anti-TFR-directed liposomes are effective for
intracellular drug delivery to ATL cells and may represent a useful method
of treatment in this disease.
Volume 74,
Issue 6,
pp. 2043-2052,
11/01/1989
Copyright © 1989 by The American Society of Hematology
