1993 Fiscal Year Final Research Report Summary
A NEW ANTI-TUMOR IMMUNOTHERAPY TARGETING HUMAN PROTO-ONCOGENE PRODUCT
| Project/Area Number |
04670752
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | TOKAI UNIVERSITY |
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Principal Investigator |
TOKUDA Yutaka TOKAI UNIV.SCHOOL OF MED., ASSISTANT PROFESSOR, 医学部, 講師 (20163975)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Adoptive immunotherapy / Proto-oncogene / C-erbB-2 / CD4^+ T cell / Bispecific antibody |
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| Research Abstract |
To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody(BSAb)containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BSAb specifically reacts with both c-erbB-2-positive tumor cells and CD3^+CTL.Human CD4^+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4^+ helper/killer cells with the BSAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4^+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BSAb. Moreover, by combination with the BSAb, CD4^+ helper/killer cells showed a significant in vivo anti-tumor effect against c-erbB-2 positive human cancer cells in severe combined immunodeficiency mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BSAb-directed adoptive tumor immunotherapy. Thus, we have established a large-scale culture system of these CD4^+ helper/killer T cells to provide enough number of the cells for future clinical trials.
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