Transplantation acute rejection

For short-term chnical interventions with the aim of protecting the kidney during acute reperfusion or preventing allograft rejection after transplantation, the prerequisite of parenteral administration does not constitute a serious limitation. 

Early clinical trials indicate that mycophenolate mofetil in conjunction with cyclosporine and corticosteroids is a more effective regimen than azathioprine in preventing the acute rejection of transplanted organs. GI side effects are most common. 

Orthoclone OKT3 CD3 Murine Acute transplant rejection... 

Simulect (Mab) Acute rejection kidney transplants Recombinant myeloma... 

Boratynska M, Banasik M, Patrzalek D, Klinger M. 2006. Conversion from cyclosporine-based immunosuppression to tacrolimus/mycophenolate mofetil in patients with refractory and ongoing acute renal allograft rejection. Ann Transplant. 11 51-56. 

About 10 days after transplantation, acute rejection of the graft begins as a result of cell-mediated immunity. Acute rejection is a result of infiltration of large numbers of macrophages and lymphocytes into the graft. Helper T-cell activation and proliferation play a major role in this process, and both complement-dependent cell-mediated cytotoxicity and ADCC are involved in the destruction of the graft. Acute rejection could be in the form of acute vascular rejection, acute cellular rejection or both. Acute vascular rejection involves the necrosis of the blood vessel cells of the graft... 

Antibodies that block the interleukin-2 receptor, thus preventing interleukin-2 from activating T lymphocytes, have also been developed.24,62 These antiinterleukin-2 receptor agents, such as basiliximab (Simulect) and daclizumab (Zenapax), may be helpful in reducing the incidence of acute transplant rejection.13 Antibodies seem to be especially useful in the initial (induction) phase of antirejection treatment because these drugs can delay or supplant the use of more toxic immunosuppressants such as the glucocorticoids and calcineurin inhibitors (cyclosporine and tacrolimus).3,56... 

Azathioprine and 6-mercaptopurine are immunosuppressants that are used for the treatement of several conditions including immunological disorders and for prevention of acute rejection in transplant recipients. In Europe, azathioprine the precursor of 6-mercaptopurine has been the thio-... 

Simulect / basiliximab mAb Acute transplanted kidney rejection Murine myeloma 1998... 

The first therapeutic antibody approved (Orthoclone OKT-3 or Muromonab CD3, 1986) was indicated not for cancer treatment, but for controlling acute rejection of transplanted organs (kidney, heart, and liver). Nowadays, other clinical indications such as asthma, rheumatoid arthritis, psoriasis, and Crohn s disease are treated with mAbs (see Chapter 17) (Antibody Engineering and Manufacture, 2005 Monoclonal Antibodies and Therapies, 2004 Hot Drugs, 2004 Walsh, 2004). 

Citterio F, Serino F, Pozzetto U, Fioravanti P, Caizzi P, Castagneto M. Verapamil improves Sandimmune immunosuppression, reducing acute rejection episodes. Transplant Proc 1996 28(4) 2174-6. 

Schnetzler B, Kondo-Oestreicher M, Vala D, Khatchatomian G, Faidutti B. Orlistat decreases the plasma level of cyclosporme and may be responsible for the development of acute rejection episodes. Transplantation 2000 70(10) 1540-1. 

MMF also has demonstrated efficacy in the treatment of acute rejection. Kidney transplant recipients converted to MMF after the first acute rej ection episode had fewer subsequent rejections compared with those who continued with azathioprine after rejection treatment. The change in therapy was associated with no increase in adverse effects or malignancies and a trend toward better graft function and survival. ... 

Tacrolimus-based immunosuppression demonstrates lower rates of acute rejection in transplantation of almost all other organs evaluated to date. 

Because of its potent immunosuppressive properties, cyclophosphamide has been used to prevent organ rejection after transplantation. It has activity in nonneoplastic disorders, including Wegener s granulomatosis, rheumatoid arthritis, and nephrotic syndrome. Caution is advised when the drug is considered for these conditions, both because of its acute toxic effects and because of its potential for inducing sterility, teratogenic effects, and leukemia. 

Immunomodulatory. Polyclonal antibody depletes T cells responsible for acute organ rejection in transplant patients. 

In contrast, rituximab (Rituxan IDEC Pharmaceuticals) is a highly targeted antibody that binds principally with CD-20-positive B lymphocytes implicated in one form of non-Hodg-kin s lymphoma. Muromonab-CD3 (Orthoclone OKT3 Ortho Pharmaceuticals), used to reverse acute rejection of transplanted kidneys, is another example of the specific type of therapeutic antibody. Specific antigens are far more common as therapeutic targets. 

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