Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
1998-01-21
2001-03-06
Budens, Robert D. (Department: 1645)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007200, C435S007210, C435S040500, C435S040510, C435S040520
Reexamination Certificate
active
06197531
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to determining the immunocompetence of a mammal and to treatments, prognoses and pharmaceutical compositions for diseases exhibiting deficient immunocompetence, e.g., HIV infection.
BACKGROUND OF THE INVENTION
Cytotoxic T-lymphocyte cells play a central role in the biological defense against what are commonly considered irreversible, pathogenic infections with human immunodeficiency virus (HIV). It is believed that, as a consequence of HIV infection, cytotoxic T-lymphocyte cells are recruited to limit the spread of viral infection by recognizing and lysing viral-infected cells. A central role in the expression of anti-viral activity of cytotoxic T-lymphocyte cells is played by a cell surface molecular receptor signaling process whereby cell surface sensing proteins detect the presence of HIV peptides contained in the viral envelope or viral-specific enzymes.
In HIV-infected individuals who have not developed AIDS opportunistic infections, there is a high frequency of circulating T cells bearing T cell receptors that recognize HIV-infected cells. Despite the vigorous expansion of antiviral T cells which can develop into cytotoxic effector cells capable of lysing HIV-infected targets and which secrete soluble factors capable of suppressing HIV replication, the cellular immune response eventually becomes unable to control viral production, the HIV-infected individual having become deficient in immunocompetence.
SUMMARY OF THE INVENTION
It is an object of the invention to provide a safe, easy and inexpensive method for determining the immunocompetence of a mammal.
It is another object of the invention to provide a method for determining the immunocompetence of a mammal which uses non-viable and non-radioactive specimens and reagents.
It is another object of the invention to provide a safe, easy and inexpensive method for monitoring a therapeutic treatment of a disease such as HIV.
It is another object of the invention to provide a safe, easy and inexpensive method for assessing the progression of a disease such as HIV.
Still another object of the invention is to provide methods for treating HIV infection in a mammal.
In one aspect, the invention features a method for determining the immunocompetence of a mammal. Bodily fluid having cells from a mammal, the cells having T cell receptor complexes, is provided. The expression of a first component, e.g., CD3&zgr;, and a second component, e.g., CD3&egr;, of the T cell receptor complexes, is evaluated. An abnormal ratio of the number of cells expressing the first component as compared to the number of cells expressing the second component indicates altered immunocompetence in the mammal.
In preferred embodiments, evaluation of expression of the first component and the second component of the T cell receptor complexes comprises contacting a first sample of the bodily fluid from the mammal with a first antibody that binds to the first component, and contacting a second sample of the bodily fluid with a second antibody that binds to the second component, under conditions which allow for formation of a first reaction complex comprising the first component and the first antibody, and a second reaction complex comprising the second component and the second antibody. The number of cells expressing the first and second complexes formed is detected. The number of cells expressing the first reaction complex corresponds to the level of the first component in the bodily fluid sample, and the number of cells expressing the second reaction complex corresponds to the level of the second component in the bodily fluid sample. The ratio of the number of cells expressing the first reaction complexes formed to the number of cells expressing the second reaction complexes formed is determined. An abnormal ratio of the number of cells expressing the first component as compared to the number of cells expressing the second component indicates altered immunocompetence in the mammal. Preferably, the antibodies are labeled with fluorescent reagents, and preferably, detection of the amount of first and second reaction complexes formed is by flow cytometry.
Another aspect of the invention is a method for monitoring a therapeutic treatment of a disease in a mammal associated with an abnormal level of a first T cell receptor complex component, e.g., HIV infection, Hodgkin's disease or a solid tumor. The ratio of cells expressing the first T cell receptor complex component and a second T cell receptor complex component in a plurality of bodily fluid samples having cells obtained at different time points from a mammal undergoing a therapeutic treatment for a disease associated with an abnormal level of the first T cell receptor complex component, is determined. A ratio that has become more normal is indicative of an effective therapeutic treatment. Preferably, the first component is CD3&zgr;. Preferably, the second component is CD3&egr;.
Another aspect of the invention is a method for assessing the progression of a disease in a mammal associated with an abnormal level of a first T cell receptor complex component. The ratio of cells expressing the first T cell receptor complex component and a second T cell receptor complex component in a plurality of blood samples having cells obtained at different time points from the mammal is determined. A ratio that becomes more abnormal is indicative of progression of the disease, and a ratio that becomes more normal is indicative of regression of the disease.
Another aspect of the invention is a method for predicting the prognosis of a mammal having a disease which is associated with an abnormal level of a first T cell receptor complex component. The ratio of cells expressing the first T cell receptor complex component and a second T cell receptor complex component in a plurality of bodily fluid samples having cells obtained at different time points from the mammal is determined. A ratio that becomes more abnormal is indicative of a negative prognosis for the mammal, and a ratio that becomes more normal is indicative of a positive prognosis for the mammal.
Another aspect of the invention is a method for determining if a mammal is at risk for AIDS. Bodily fluid having cells from a mammal, the cells having T cell receptor complexes, and the mammal being infected with HIV, is provided. The ratio of cells expressing a first T cell receptor complex component and a second T cell receptor complex component is determined. An abnormal ratio is diagnostic of being at risk for AIDS.
Another aspect of the invention is a method for evaluating an agent for use in treating HIV infection. A mammal infected with HIV is provided. The mammal has an abnormal ratio of the number of cells expressing a first T cell receptor complex component as compared to the number of cells expressing a second T cell receptor complex component. An agent is provided. The agent is administered to the mammal in a therapeutically effective amount. The effect of the agent on the ratio of the number of cells expressing the first T cell receptor complex component as compared to the number of cells expressing the second T cell receptor complex component is evaluated. A change in the ratio is indicative of the usefulness of the agent in treating HIV infection.
Another aspect of the invention is a method for treating HIV infection in a mammal. A mammal having T cell receptor complexes and in need of treatment for HIV infection is provided. An agent capable of altering the expression of a signaling component of the T cell receptor complex is provided. The agent is administered to the mammal in a therapeutically effective amount such that treatment of the HIV infection occurs.
Another aspect of the invention is a method for treating HIV infection in a mammal. A mammal having T cell receptor complexes and in need of treatment for HIV infection is provided. T cells which have been cultured under conditions so as to increase the expression of a signaling component of the T cell receptor complexes to a level such that T cel
Budens Robert D.
Center For Blood Research, Inc.
Fish & Richardson P.C.
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