KUSAMA Mikio Tokyo Medical and Dental University, Faculty of Dentistry, Research associate, 歯学部, 助手 (60124690)
FUJIBAYASHI Takashi Tokyo Medical and Dental University, Faculty of Dentistry, Assistant prof., 歯学部, 講師 (80013978)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1989 : ¥1,600,000 (Direct Cost : ¥1,600,000)
A Grest number of cells, which have high level of cytotoxic activity, are demanded for successful adoptive immunotherapy with Lymphokine-Activated Killer (LAK) cells. We attempted to make culture CD3-LAK cells using anti-CD3 monoclonal antibody and interleukin-2, and investigated how the proliferative response and cytotoxic activity of LAK cells (CD3・LAK) are affected by BRM (cytokines, OK432, etc.). In clinically, therapeutic effects of the combination of radiation therapy, chemotherapy and adoptive immunotherapy are expected, therefor, we investigated the effect of these therapy on CD3-LAK cells.
1. Induction of CD3・LAK cells : High proliferative response and cytotoxic activity were induced from peripheral blood lymphocytes (PBL) by using anti-CD3 monoclonal antibody and IL-2.
2. The effect of cytokines (rIFNgamma, rTNF alpha, rG-CSF, rIL-1 alpha, rIL-1beta) on CD3・LAKcells : Proliferative response of CD3・LAK cells increased by rTNFalpha at low concentration of rIL-2. Cytotoxic activity of these cells were not affected by any cytokines. At the first stage of CD・LAK induction, OK432 significantly enhanced cytotoxic activity of these cells.
3. The effect of antineoplastic agent (CDDP, 5-FU, MTX, PEP, BLM, ADR) and irradiation (1.25, 2.5, 5.0, 10.0, 20.0Gy) on CD3・LAK cells : Proliferative response of CD3-LAK cells were suppressed by both antineoplastic agent and irradiation.Cytotoxic activiy of these cells were neither affected by antineoplastic agent nor irradiation.
These results indicate that LAK induction using together anti-CD3 monoclonal antibody with rIL-2 is available for adoptive immunotherapy on oral cancer patients, and that therapeutic effects of adoptive immunotherapy in combination with chemotherapy and radiation therapy are expected.