Bispecific antibody-mediated cytotoxicity by CD4+ and CD8(+)-activated T cells generated from leukemia patients after allogeneic bone marrow transplantation.
The F(ab')2 bispecific antibody (BSAb) was prepared from anti-CD3 moAb and anti-CD10 moAb. The BSAb could react with both CD3+ T cells and CD10+ leukemia cells and triggered T cell-mediated cytotoxicity. To apply the BSAb to prevention of leukemic relapse after BMT, we investigated the generation of both CD4+ and CD8+ anti-tumor effector T cells from patient's PBMC 14 days after BMT. Neither CD4+ T cells nor CD8+ T cells, which were activated with immobilized anti-CD3 moAb plus IL-2, could lyse CD10+ leukemia cells by themselves, but they showed augmented cytotoxicity against CD10+ leukemia cells by targeting with anti-CD3 x anti-CD10 BSAb. Moreover, the activated CD4+ T cells were demonstrated to produce IL-2 and IFN-gamma when they were cultured with CD10+ leukemia cells in the presence of the BSAb. The BSAb-mediated cytotoxicity of activated T cells was demonstrated not only against the recipient leukemia cells but also against third party leukemia cells. These results suggested that anti-CD3 x anti-CD10 BSAb might be a good tool to prevent relapse after BMT in combination with activated CD4+ T cells and CD8+ T cells.
Hattori
K
K
Department of Pediatrics, Tokai University School of Medicine, Isehara, Japan.
Tsukamoto
H
H
Ohta
S
S
Yabe
M
M
Yabe
H
H
Kato
S
S
Takakura
I
I
Ueda
R
R
Habu
S
S
Nishimura
T
T
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007938:Leukemia / Q000601:surgery; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D015260:Neprilysin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015260:Neprilysin