1989 Fiscal Year Final Research Report Summary
Anti-human LFA-1 monoclonal antibodies for prevention of graft failure in HLA-mismatched bone marrow transplantation.
| Project/Area Number |
63480233
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
KONNO Tasuke Tohoku University, Research Institute for Tuberculosis and Cancer Professor, 抗酸菌病研究所, 教授 (00004846)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAGUTI Yosiko Tohoku University, Research Institute for Tuberculosis and Cancer, 抗酸菌病研究所, 医員
MINEGISHI Masayoshi Tohoku University, Research Institute for Tuberculosis and Cancer Instructor, 抗酸菌病研究所, 助手 (20211592)
SATO Tetsuo Tohoku University, Research Institute for Tuberculosis and Cancer Instructor, 抗酸菌病研究所, 助手 (90170761)
TSUCHIYA Sigeru Tohoku University, Research Institute for Tuberculosis and Cancer Associate Prof, 抗酸菌病研究所, 助教授 (30124605)
|
|---|
| Project Period (FY) |
1988 – 1989
|
| Keywords | bone marrow transplantation / LFA-1 / graft rejection / HLA-mismatch / monoclonal antibody |
|---|
| Research Abstract |
1. Use of the anti-LFA-1 antibody to prevent graft failure in HLA-haplotype mismatched bone marrow transplantation (BMT). A patient with Fanconi anemia underwent T cell- devpleted HLA-haplotype mismatched maternal BMT because of the lack of HLA-identical donor. To prevent graft failure a murine monoclonal antibody (mAb) directed against the alpha chain of human LFA-1 was used. The mAb (25.3) was kindly supplied by Immunotech (Marseille, France). The antibody preparations were checked for sterility and lack of pyrogenicity. The mAb was given in a 6-h iv infusion m dosis of 0.1 mg/kg for consecutive days from-3 to +6 without any signs of adverse reactions. Partial;hematological reconstitution was achieved but finally resulted in graft failure. The result in Fanconi anemia is in accord with experiences in other institutions. However, no adverse reactions in the use of the anti-LFA-1 mAb encourage to continue further clinical studies in patients selected.
2. Production of mAb against human LFA-1. To obtain anti-LFA-1 mAb capable of inducing immune tolerance and available for clinical use spleen cells from BALB/C mice immunized with K4 cells were fused with SP2/0 cells. Hybridoma supernatants obtained were screened for the capability of inhibiting the aggregation of K4 cells stimulated by phorbol ester.
Three hybridoma clones secreting anti-LFA-1 antibodies were obtained; one clone was determined by flowcytometry and biochemical analysis to produce the antibody directed at a chain (MAY-035) and other two the antibodies directed at 8 chain (MAY-017, and MAY-044). The isotype of the mAbs obtained was all IgGl. The three antibodies strongly inhibited lymphocyte proliferation in response to alloantigens and mitogens.
|
