Bispecific antibody-mediated cytotoxicity by CD4+ and CD8 (+) -activated T cells generated from leukemia patients after allogeneic bone marrow transplantation
Hattori, K.; Tsukamoto, H.; Ohta, S.; Yabe, M.; Yabe, H.; Kato, S.; Takakura, I.; Ueda, R.; Habu, S.; Nishimura, T.
Bone Marrow Transplantation 15(2): 193-198
1995
ISSN/ISBN: 0268-3369 PMID: 7773208 Document Number: 440840
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 times 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 times anti-CD10 BSAb might be a good tool to prevent relapse after BMT in combination with activated CD4+ T cells and CD8+ T cells.