Immunex Corporation

Targeted Genetics Corporation

Sterling Winthrop Inc.

Sanofi

Sanofi-synthelabo

Stephen D Lupton

Raymond G Goodwin

Diane Y Mochizuki

Anthony E Namen

John Ernest Sims

David J Cosman

Bruce A Mosley

Steven K Dower

James Maurice Allen

Andrew Lawrence Feldhaus

Anthony M Stepan

Tineka J Quinton

Recombinant vectors are provided that render the proliferative response of activated lymphocytes, particularly cytotoxic T lymphocytes, of lessened dependency on T helper cells. The vectors are comprised of a region encoding a stimulatory factor polypeptide operably linked to a heterologous transcriptional control region. Expression of the stimulatory factor polypeptide from the recombinant polynucleotide in an activated lymphocyte renders the proliferative response of less dependent on lymphocyte T helper cells. When the lymphocyte is activated by binding of its cognate antigen the transcriptional control region causes transcription of the stimulatory factor encoding region. The cells containing the vector, particularly CTLs, are of use in immunotherapy.

Hybrid genes for expression of stimulatory factors in activated T cells

The invention provides selectable fusion genes including a dominant positive selectable gene fused to and in reading frame with a negative selectable gene. The selectable fusion gene encodes a single bifunctional fusion protein which is capable of conferring a dominant positive selectable phenotype and a negative selectable phenotype on a cellular host. A dominant positive selectable phenotype is conferred, for example, by the hph gene for hygromycin B resistance (Hm ). A dominant negative selectable phenotype is conferred, for example, by the HSV-I TK gene for ganciclovir sensitivity (GCV ). A dominant positive selectable phenotype is also conferred by the neo gene for G-418 aminoglycoside antibiotic resistance (G-418 ). A dominant negative selectable phenotype is also conferred by the CD gene for 5-fluorocytosine sensitivity (5-FC ). The present invention also provides recombinant expression vectors, such as retroviral vectors, which include selectable fusion genes, and cells transduced with the recombinant expression vectors. The bifunctional selectable fusion genes are expressed and regulated as a single genetic entity, permitting co-regulation and co-expression with a high degree of efficiency.

Bifunctional selectable fusion genes

The present invention provides AAV &ldquo;split-packaging&rdquo; genes, and packaging cells comprising such genes, for use in the production of high titers of replication-incompetent recombinant AAV vectors that can be used to deliver transgenes of interest to a variety of mammalian cells.

AAV split-packaging genes and cell lines comprising such genes for use in the production of recombinant AAV vectors

Type II IL-1 receptor (type II IL-1R) proteins, DNAs and expression vectors encoding type II IL-1R, and processes for producing type II IL-1R as products of recombinant cell culture, are disclosed.

Type II Interleukin-1 receptors

DNA encoding type II IL-1 receptors

Mammalian Interleukin-7 proteins (IL-7s), DNAs and expression vectors encoding mammalian IL-7s, and processes for producing mammalian IL-7s as products of cell culture, including recombinant systems, are disclosed.

Use of interleukin-7 to stimulate proliferation of hematopoietic cell

Mammalian Interleukin-7 proteins (IL-7s)g DNAs and expression vectors encoding mammalian IL-7s, end processes for producing mammalian IL-7s as products of cell culture, including recombinant systems, are disclosed.

Hybrid genes for use in the production of T.sub.H -independent cytotoxic

Type II IL-1 receptor (type II IL-1R) proteins, DNAs and expression vectors encoding type II IL-1R, and processes for producing type II IL-1R as products of recombinant cell culture, are disclosed. Also disclosed are compositions and methods for regulating an IL-1 mediated immune or inflammatory response in a mammal.

Soluble type II interleukin-1 receptors and methods

Antibodies that are immunoreactive with interleukin-7 (IL-7) proteins are provided. The anti-IL-7 antibodies may be polyclonal or monoclonal. Certain embodiments are directed to antibodies that are immunoreactive with human IL-7.

Growing community of inventors

Seattle, WA, United States of America

Stephen D Lupton