Drug – bio-affecting and body treating compositions – Lymphokine
Patent
1992-05-07
1993-02-02
Lee, Lester L.
Drug, bio-affecting and body treating compositions
Lymphokine
A61K 39395
Patent
active
051836572
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to antibodies against human alpha (.alpha.)-tumour necrosis factor for use in antilymphocyte antibody therapy, to therapeutic compositions containing an antibody against human .alpha.-tumour necrosis factor and an antilymphocyte antibody, and to recombinant antibodies against human .alpha.-tumour necrosis factor.
BACKGROUND TO THE INVENTION
Antilymphocyte antibody therapy has become a recognised clinical technique for use when it is desired to supplement or modify the normal immune response in humans. Thus, for example, the intravenous administration of polyclonal rabbit or horse antilymphocyte antibodies is an effective treatment for acute kidney allograft rejection. More recently, monoclonal antilymphocyte antibodies, such as Orthoclone OKT3, have been used for this purpose.
Despite the effectiveness of antilymphocyte antibody therapy, treatment has been hindered in many cases by the occurence of shock-related side effects, making it necessary to temporarily discontinue the antibody infusion. Side effects include fever and chills, arthralgias, nausea and vomiting, tachycardia, angina pectoris, dyspnoea due to bronchospasm, and, in the case of OKT3 infusion, pulmonary oedema. In addition to the discomfort these side effects can cause, the severity of some of the effects precludes the use of antilymphocyte antibody therapy in some patients, for example people with pulmonary or cardiac disease.
We have now found that patients who are undergoing antilymphocyte antibody therapy, and who are also experiencing shock-related side effects, have surprisingly high plasma levels of .alpha.-tumour necrosis factor (.alpha.-TNF). We have used this to develop means to control shock-related conditions arising from antilymphocyte antibody therapy.
SUMMARY OF THE INVENTION
Thus, according to one aspect of the invention we provide an antibody against human .alpha.-tumour necrosis factor for use in the prevention or treatment of shock-related conditions arising from antilymphocyte antibody therapy.
The term antilymphocyte antibody therapy as used herein is especially to be understood to mean the use of an antilymphocyte antibody in the prophylaxis or treatment of immunoregulatory disorders in which rejection of self or non-self tissue occurs, for example in autoimmune diseases such as thyroiditis or rheumatoid arthritis, or, in particular, in a rejection episode following an organ or tissue transplant.
The shock-related conditions which may arise from antilymphocyte antibody therapy and which may be prevented or treated according to the present invention may be any physiological conditions which are generally associated with a degree of circulatory collapse. Particular conditions include, for example, cardiac conditions such as tachycardia and angina, e.g. angina pectoris; pulmonary conditions such as bronchospasm; musculo-skeletal conditions, for example joint pains such as arthralgia; and general metabolic disorders such as oedema, e.g. pulmonary oedema, and abnormal body temperatures.
The antibodies against human .alpha.-tumour necrosis factor (hereinafter referred to as anti-TNF.alpha. antibodies) for use according to the invention may in general belong to any immunoglobulin class. Thus for example the anti-TNF.alpha. antibody may be an immunoglobulin G or immunoglobulin M antibody.
The anti-TNF.alpha. antibody may be of animal, for example mammalian origin and may be for example of murine, rat or human origin. The antibody may be a whole immunoglobulin, or a fragment thereof, for example a fragment derived by proteolytic cleavage of a whole antibody, such as F(ab').sub.2, Fab' or Fab fragments, or fragments obtained by recombinant DNA techniques, for example Fv fragments (as described in International Patent Application No. PCT/GB 88/00747).
The anti-TNF.alpha. antibody may be polyspecific but is preferably monospecific for human .alpha.-TNF. The antibodies may be polyclonal or monoclonal antibodies. Particularly useful antibodies for use according to the invention in
REFERENCES:
Chemical Abstracts, abstract 154301t, vol. 106, 1987.
Robinson, Muromonab-CD3 (Orthoclone OKT3.RTM.)-A Review, Drugs of Today, pp. 603-609, vol. 22, No. 12, 1986.
Debets et al Transplantation, vol. 47, No. 3 pp. 487-492, Mar. 1989.
Tracey et al Nature, vol. 330 Dec. 17, 1987 pp. 662-664.
Celltech Limited
Koh Choon P.
Lee Lester L.
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