The Immune Response Corporation

Avant Immunotherapeutics, Inc.

Dennis J Carlo

Steven W Brostoff

Mark D Howell

Jonas Salk

Henry C Chiou

Daniel P Gold

Darcy B Wilson

Deborah J Kwoh

Lawrence R Smith

Jennie C C Chang

The present invention provides a method for increasing HDL cholesterol in a mammal by stimulating an immune response that inhibits the function of CETP. Such an immune response can be induced by immunizing with CETP or fragments of CETP (together termed 'CETP Peptides') which contain an epitope capable of stimulating such a response. The peptides can be conjugated to a carrier, such as KLH or ovalbumin, in order to increase immunogenicity. Adjuvants can also be administered.

Method for increasing HDL cholesterol level

The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. The vaccine is administered to the mammal in a manner that induces an immunologically effective response so as to affect the course of the disease. The invention additionally provides specific &bgr;-chain variable regions of the T cell receptor, designated V&bgr;6.2/3, V&bgr;6.5, V&bgr;2, V&bgr;5.1, V&bgr;13 and V&bgr;7, which are central to the pathogenesis of multiple sclerosis (MS).

Vaccination and methods against multiple sclerosis resulting from pathogenic responses by specific T cell populations

This invention relates to methods of preventing or reducing the severity of psoriasis. In one embodiment, the method involves administering to the individual a peptide having substantially the sequence of a non-conserved region sequence of a T cell receptor, present on the surface of T cells mediating psoriasis or a fragment thereof, wherein the peptide or fragment is capable of causing an effect on the immune system to regulate the T cells. In particular, the T cell receptor has the V&bgr; region-V&bgr;3, V&bgr;13.1 or V&bgr;17. In another embodiment, the method involves gene therapy. The invention also relates to methods of diagnosing psoriasis by determining the presence of psoriasis predominant T cell receptors.

Peptides and methods against psoriasis

A molecular complex comprising a gene encoding interferon releasably linked to a conjugate of a nucleic acid binding agent and a ligand which binds to a component on the surface of a cell. In a preferred embodiment, the gene encodes human IFN-&agr;, IFN-&bgr;, or IFN-&ggr;. The complex can be used to obtain targeted expression of interferon in selected cells either in vivo or in vitro.

Targeted delivery of genes encoding interferon

The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific &bgr;-chain variable regions of T cell receptors, designated V&bgr;3, V&bgr;4, V&bgr;12, V&bgr;14 and V&bgr;17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

Method of preventing the proliferation of V&bgr;14 or V&bgr;17-Expressing T cells

The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens complexed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific &bgr;-chain variable regions of T cell receptors, designated V&bgr;3, V&bgr;4, V&bgr;12, V&bgr;14 and V&bgr;17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

Vaccination and methods against diseases resulting from pathogenic responses by specific T cell populations

The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the mammal in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides a specific .beta.-chain variable region of the T cell receptor, designated V.beta.17, which is central to the pathogenesis of rheumatoid arthritis (RA). Also provided are means to detect, prevent and treat RA.

Vaccination and methods against diseases resulting from pathogenic

The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides specific .beta.-chain variable regions of T cell receptors, designated V.beta.3, V.beta.4, V.beta.12, V.beta.14 and V.beta.17, which are associated with the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Also provided are means to detect, prevent and treat RA and MS. Methods of administering DNA or RNA encoding the polypeptides useful as vaccines of the present invention into the tissue cells of an individual is also provided.

A molecular complex comprising a gene encoding interferon releasably linked to a conjugate of a nucleic acid binding agent and a ligand which binds to a component on the surface of a cell. In a preferred embodiment, the gene encodes human IFN-.alpha., IFN-.beta., or IFN-.gamma.. The complex can be used to obtain targeted expression of interferon in selected cells either in vivo or in vitro.

The present invention provides a non-infectious immunotherapeutic containing retroviral particles devoid of outer envelope proteins or containing selected antigens isolated from a retrovirus. There is also provided a vaccine effective against HIV. In one aspect, the immunogen is useful for immunizing an individual previously infected by a retrovirus including HIV, so as to induce immunoprotective factors protective against progression of the infection. In another aspect, the vaccine is useful for vaccinating an individual not previously infected with HIV in order to prevent subsequently acquired infection. In another aspect, there is provided a method of rendering a viral immunogen non-infectious. The immunogen may also be used to produce antibodies for passive immunotherapy, alone or in conjunction with active immunotherapy, in individuals infected with a retrovirus, including HIV, preferably those individuals exhibiting low levels of antibodies to retroviral gene products other than the outer envelope.

Prevention and treatment of retroviral disease

The present invention provides vaccines and a means of vaccinating a host so as to prevent or control specific T cell mediated pathologies. The vaccine is composed of anti-idiotypic antibodies which are internal images of a segment of the T cell receptor (TCR) present on the surface of the pathogenic T cells. The vaccine is administered to the host in a manner that induces an immune response directed against the TCR of pathologic T cell. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. Means of determining an appropriate amino acid sequence for such a vaccine are also provided.

Anti-idiotype vaccination against diseases resulting from pathogenic

The present invention provides a non-infectious immunotherapeutic containing retroviral particles devoid of outer envelope proteins or containing selected antigens isolated from a retrovirus. There is also provided a vaccine effective against HIV. In one aspect, the immunogen is useful for immunizing an individual previously infected by a retrovirus including HIV, so as to induce immunoprotective factors protective against progression of the infection. In another aspect, the vaccine is useful for vaccinating an individual not previously infected with HIV in order to prevent subsequently acquired infection. In another aspect, there is provided a method of rendering a viral immunogen non-infectious. The immunogen may also be used to produce is antibodies for passive immunotherapy, alone or in conjunction with active immunotherapy, in individuals infected with a retrovirus, including HIV, preferably those individuals exhibiting low levels of antibodies to retroviral gene products other than the outer envelope.

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Rancho Santa Fe, CA, United States of America

Dennis J Carlo