Human gammadelta(+) T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response.
Refractory acute lymphoblastic leukemia (ALL) is often incurable, and relapse rates following allogeneic bone marrow transplantation (BMT) remain high. We have reported that patients who develop increased numbers of gammadelta(+) T cells soon after BMT are significantly less likely to relapse. We now show in seven donor/recipient pairs that donor-derived Vdelta1(+)CD4(-)CD8(-)gammadelta(+) T cells are activated and proliferate in response to recipient primary ALL blasts. In addition, these cells have been shown to bind and lyse the recipient ALL blasts. Separately, gammadelta(+) T cells proliferate poorly or not at all in mixed lymphocyte culture against HLA-mismatched unrelated stimulator cells. These observations suggest that allogeneic gammadelta(+) T cells could be an effective immunotherapeutic strategy against refractory disease without the risk of graft-versus-host disease.
Lamb
L S
LS
University of South Carolina, South Carolina Cancer Center, Columbia 29203, USA.
Musk
P
P
Ye
Z
Z
van Rhee
F
F
Geier
S S
SS
Tong
J J
JJ
King
K M
KM
Henslee-Downey
P J
PJ
D003602:Cytotoxicity, Immunologic; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007959:Lymphocyte Culture Test, Mixed; D008222:Lymphokines / Q000502:physiology*; D009000:Monocytes / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000628:therapy; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D008222:Lymphokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; C022780:allogenic effect factor