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Blood, Vol. 93 No. 7 (April 1), 1999:
pp. 2336-2341
Feasibility of Immunotherapy of Relapsed Leukemia With Ex
Vivo-Generated Cytotoxic T Lymphocytes Specific for Hematopoietic
System-Restricted Minor Histocompatibility Antigens
Tuna Mutis,
Rob Verdijk,
Ellen Schrama,
Bennie Esendam,
Anneke Brand, and
Els Goulmy
From the Department of Immunohematology and Blood Bank, Leiden
University Medical Center, Leiden, The Netherlands.
Allogeneic bone marrow transplantation (BMT) is a common treatment
of hematologic malignancies. Recurrence of the underlying malignancy is
a major cause of treatment failure. Donor-derived cytotoxic T
lymphocytes (CTLs) specific for patients' minor histocompatibility antigens (mHags) play an important role in both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) reactivities. mHags HA-1
and HA-2 induce HLA-A*0201-restricted CTLs in vivo and are exclusively
expressed on hematopoietic cells, including leukemic cells and leukemic
precursors, but not on fibroblasts, keratinocytes, or liver cells. The
chemical nature of the mHags HA-1 and HA-2 is known. We investigated
the feasibility of ex vivo generation of mHag HA-1- and HA-2-specific
CTLs from unprimed mHag HA-1- and/or HA-2-negative healthy blood
donors. HA-1 and HA-2 synthetic peptide-pulsed dendritic cells (DCs)
were used as antigen-presenting cells (APC) to stimulate autologous
unprimed CD8+ T cells. The ex vivo-generated HA-1- and
HA-2-specific CTLs efficiently lyse leukemic cells derived from acute
myeloid leukemia (AML) and acute lymphoid leukemia (ALL) patients. No
lytic reactivity was detected against nonhematopoietic cells.
Sufficient numbers of the CTLs can be obtained for the adoptive
immunotherapy purposes. In conclusion, we present a feasible, novel
therapy for the treatment for relapsed leukemia after BMT with a low
risk of GVHD.
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