University of Texas System

Baylor College of Medicine

Ralph B Arlinghaus

Gabriel Lopez-Berestein

Pramod N Nehete

Ana Maria Tari

Jack A Roth

Lin Ji

Jagannadha K Sastry

Bulent Ozpolat

Chris D Platsoucas

Jacki Lin

K Jagannadha Sastry

Jiaxin Liu

Tong Sun

Dai Lu

James T Sparrow

Jean Y Wang

Jie O Guo

Jagannada K Sastry

Victor A Dwyer, Iv

Yun Wu

A nanoparticle-polypeptide complex comprising a bioactive polypeptide in association with a nanoparticle, wherein the bioactive polypeptide is modified by the addition of a chemical moiety that facilitates cellular uptake of the protein. The polypeptide can be a protein or a peptide. In some embodiments, the amino acid sequence of the protein or peptide is derived from the amino acid sequence of a tumor suppressor gene product.

Bioactive FUS1 peptides and nanoparticle-polypeptide complexes

The present invention provides novel compositions and methods for use in the treatment of cancer, specifically, in the treatment of chronic myelogenous leukemia (CML). The compositions contain antisense oligonucleotides that hybridize to Grb2 and Crkl nucleic acids, the gene products of which are known to interact with the tumorigenic protein bcr-abl. Used alone, in conjunction with each other, and even in conjunction with antisense oligonucleotides directed to bcr-abl nucleic acids, these compositions inhibit the proliferation of CML cancer cells.

Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to Grb2 or Crk1

Disclosed are compositions and methods for the prevention and treatment of viral infections. The identification of distinct classes of peptides for use in both anti-viral vaccines and therapeutic formulations is reported. Peptide formulations are disclosed which enhance the systemic distribution, activity, and longevity of anti-viral cytotoxic T cells, and/or which protect human cells from HIV infection.

Compositions and methods for eliciting immune or anti-infective responses

The present invention provides novel compositions and methods for use in the treatment of cancer, specifically, in the treatment of chronic myelogenous leukemia (CML). The compositions contain antisense oligonucleotides that hybridize to Grb2 and Crk1 nucleic acids, the gene products of which are known to interact with the tumorigenic protein bcr-abl. Used alone, in conjunction with each other, and even in conjunction with antisense oligonucleotides directed to bcr-abl nucleic acids, these compositions inhibit the proliferation of CML cancer cells.

Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to GRB2 or CRK1

This invention discloses diagnostic, preventative, and treatment therapies of AIDS involving determining whether a subject exhibits an HLA-Cw7-restricted CTL response. Some methods are directed to the use of HLA-Cw7 as a genetic marker for long-term non-progression and amenability to treatment therapies. Diagnostic methods include a method for predicting long term non-progression in an HIV-infected subject. Preventative and treatment methods encompass determining whether a subject exhibits or can exhibit an HLA-Cw7-restricted CTL response. They also encompass ways of eliciting such a response, if necessary. Furthermore, some of the methods involve administering one or more HIV polypeptides or peptides, or polynucleotides encoding them, as a treatment therapy to prevent the development of AIDS.

HIV-specific T-cell induction

The present invention provides methods for detecting and quantitating BCR-ABL gene products and other abnormal ABL gene products of Ph -positive leukemic cells. The invention further provides methods for determining the relative number of leukemic cells compared with normal ABL cells to assess the tumor burden of a patient. In another aspect, the methods of the present invention can be used to determine a specific phase of leukemia, particularly chronic-phase CML.

BCR-ABL directed compositions and uses for inhibiting Philadelphia chromesome stimulated cell growth

An active peptide consisting essentially of 7 to about 30 residue and having a sequence that corresponds to a conserved domain of an HIV protein is disclosed, as is a multimer containing that peptide, an aqueous composition containing the multimer and methods of using and making the same. The aqueous composition containing an immunologically effective amount of an active peptide multimer, when introduced into an immunocompetent host animal in an immunologically effective amount, is capable of inducing cellular immunity against the native HIV protein to which the active peptide of the multimer corresponds in sequence, but is not capable of inducing production of antibodies that immunoreact with that native HIV protein.

Prophylaxis and therapy of acquired immunodeficiency syndrome

The present invention discloses a novel method for the rapid screening of candidate cytotoxic T lymphocyte- (CTL-) inducing compounds, such as peptides, by the in vivo priming of CTLs with synthetic peptides. The use of compounds so identified for the development of CTL vaccines for the treatment of various infectious disorders, including the treatment of viral diseases such as AIDS, herpes, influenza, and feline or bovine leukemia, is also disclosed, as is the use of this methodology for the preparation of specifically primed CTLs.

Methods and compositions for the priming of specific cytotoxic T-lymphocyte response

Compositions comprising a mixture of peptides that bind to molecules involved in Bcr-Abl oncoprotein function are disclosed. In addition, expression of functional BCR protein (p160 BCR) or amino terminal fragments thereof (159, 221 and 413 amino terminal residues) by way of retrovirus vectors will oppose the biological function of Bcr-Abl (p160 BCR) or inactivate Bcr-Abl tyrosine kinase function or its signal transduction function. Bcr and Abl peptides, either tyrosine phosphorylated or unphosphorylated, that bind to a region near the amino terminus of Bcr to prevent formation of tetramer Bcr-Abl molecules, that bind to the SH2 domain of Grb2, to sites on tyrosine phosphorylated Shc protein, to sites of Crkl, and to an SH2 domain of Ras Gap comprise particular peptide preparations of the invention. The peptides and polypeptides inhibit Bcr-Abl oncoprotein activation, or block the oncogenic signal generated by the Bcr-Abl oncoprotein and, thereby, inhibit growth and induce cell death of leukemia cells expressing the oncoprotein. Methods for processing bone marrow using the peptide and polypeptide compositions of the invention are also provided. Stem cells present in bone marrow may thus be enriched for Philadelphia chromosome-negative cells prior to transplantation, particularly as part of autologous bone marrow transplant therapy of leukemia, including CML, ALL and AML.

Bcr-Abl directed compositions and uses for inhibiting Philadelphia

Disclosed are compositions and methods for use in viral binding and inactivation and in protecting cells from viral infection, particularly, for use in protecting target human CD4.sup.+ cells from infection by HIV. Peptides including short sequences from CD4 are identified as being particularly effective at binding to gp120 and inhibiting or reducing HIV infection of human CD4.sup.+ cells by steric hinderance or catalytic inactivation of gp120. The invention thus encompasses improved CD4-based peptide compositions and therapeutic formulations with viral binding and HIV-inhibitory activity.

CD4 peptides for binding to viral envelope proteins

The present invention provides methods for detecting and quantitating BCR-ABL gene products and other abnormal ABL gene products of Ph.sup.1 -positive leukemic cells. The invention further provides methods for determining the relative number of leukemic cells compared with normal ABL cells to assess the tumor burden of a patient. In another aspect, the methods of the present invention can be used to determine a specific phase of leukemia, particularly chronic-phase CML.

Methods for the detection of BCR-ABL and abnormal ABL proteins in

An active peptide consisting essentially of 7 to about 30 residence and having a sequence that corresponds to a conserved domain of an HIV protein is disclosed, as is a multimer containing that peptide, an aqueous composition containing the multimer and methods of using and making the same. The aqueous composition containing an immunologically effective amount of an active peptide multimer, when introduced into an immunocompetent host animal in an immunologically effective amount, is capable of inducing cellular immunity against the native HIV protein to which the active peptide of the multimer corresponds in sequence, but is not capable of inducing production of antibodies that immunoreact with that native HIV protein.

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Bellaire, TX, United States of America

Ralph B Arlinghaus