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Reversal of transplant rejection by monoclonal antiblast antibody
Abstract:
The first clinical trial of an antiblast monoclonal antibody, CBL1, in the treatment of kidney allograft rejection is described. The theory that this antibody might destroy active clones of cells without major side effects was given validity by a previously described study showing prolongation of skin allograft survival in rhesus monkeys. CBL1 was used to treat kidney allograft rejections in 11 patients with a one-haplotype-identical related-donor graft who had been prestimulated with donor-specific transfusions and 8 patients with cadaver grafts who had been prestimulated with multiple transfusions. 15 of the rejections were steroid-resistant. Although CBL1 had no effect on the peripheral blood lymphocyte counts, rejections were reversed in 17 of 19 patients. There was 1 graft loss in the 11 recipients of related-donor grafts and 3 in patients with cadaver-donor grafts. Side effects associated with administration of antilymphocyte serum--ie, chills, fever, and thrombocytopenia--did not develop in any of the patients treated with CBL1. It is postulated that administration of an antiblast monoclonal antibody during rejection of a kidney kills only those cells that are reacting against the graft. This could result in the maintenance of normal lymphocyte numbers and immunological functions against other antigens.
Insights
The novel antiblast monoclonal antibody CBL1 effectively reversed kidney transplant rejection in 17 of 19 patients. This treatment showed minimal side effects, unlike traditional therapies, preserving immune function.
Area of Science:
- Immunology
- Nephrology
- Transplantation
Background:
- Kidney allograft rejection poses a significant challenge in transplantation.
- Steroid-resistant rejections often require alternative treatment strategies.
- Antilymphocyte serum can cause significant side effects.
Purpose of the Study:
- To evaluate the efficacy and safety of the antiblast monoclonal antibody CBL1 in treating kidney allograft rejection.
- To determine if CBL1 can reverse rejection without causing major side effects.
Main Methods:
- A clinical trial involving 19 patients with kidney allograft rejection was conducted.
- Patients received the antiblast monoclonal antibody CBL1.
- 15 of the rejections were steroid-resistant.
Main Results:
- CBL1 reversed rejection in 17 out of 19 patients.
- No significant side effects like chills, fever, or thrombocytopenia were observed.
- Graft loss occurred in 1 of 11 related-donor recipients and 3 of 8 cadaver-donor recipients.
Conclusions:
- The antiblast monoclonal antibody CBL1 is a promising treatment for kidney allograft rejection.
- CBL1 demonstrates a favorable safety profile compared to antilymphocyte serum.
- CBL1 may selectively eliminate reactive cells, preserving overall immune function.