Abstract: Chimeric T cell receptors (TCR) are provided that combine, in a single chimeric species, the intracellular domain of CD3 &zgr;-chain, a signaling region from a costimulatory protein such as CD28, and a binding element that specifically interacts with a selected target. When expressed, for example in T-lymphocytes from the individual to be treated for a condition associated with the selected target, a T cell immune response is stimulated in the individual to the target cells. The chimeric TCR's are able to provide both the activation and the co-stimulation signals from a single molecule to more effectively direct T-lymphocyte cytotoxicity against the selected target and T-lymphocyte proliferation.

Abstract: New mutant forms of human dihydrofolate reductase (DHFR) which have properties superior to the previously disclosed mutants have mutations at both amino acid 22 and amino acid 31. Specific mutant forms are Ser31Tyr22, Ser31Phe22, Gly31Tyr22, Gly31Phe22, Ala31Tyr22 and Ala31Phe22. The mutant DHFR of the invention maybe used as a selectable marker, and to modify the genome of human cells, particularly bone marrow cells or peripheral blood stem cells, to render them resistant to chemotherapy using antifolate agents.

Abstract: Recombinant antibody constructs comprise the variable regions of the heavy and light chains of anti-GD2 antibodies. These antibody constructs may be coupled to a label such as a radiolabel or to a protein such as streptavidin or pro-drug converting enzymes for use in imaging or therapeutic applications. The antibody constructs may also be transduced into T cells to produce populations of T cells which target GD2-producing tumor cells.

Abstract: Recombinant lentiviral vectors having a region encoding a functional &bgr;-globin gene; and large portions of the &bgr;-globin locus control regions which include DNase I hypersensitive sites HS2, HS3 and HS4 provides expression of &bgr;-globin when introduced into a mammal, for example a human, in vivo. Optionally, the vector further includes a region encoding a dihydrofolate reductase. The vector may be used in treatment of hemoglobinopathies, including &bgr;-thalessemia and sickle-cell disease. For example, hematopoietic progenitor or stem cells may be transformed ex vivo and then restored to the patient. Selection processes may be used to increase the percentage of transformed cells in the returned population. For example, a selection marker which makes transformed cells more drug resistant than un-transformed cells allows selection by treatment of the cells with the corresponding drug.

Abstract: The invention provides an artificial antigen presenting cell (AAPC) comprising a eukaryotic cell expressing an antigen presenting complex comprising a human leukocyte antigen (HLA) molecule of a single type, at least one exogenous accessory molecule and at least one exogenous T cell-specific epitope. Methods of use for activation of T lymphocytes are also provided.

Abstract: Recombinant antibody constructs comprise the variable regions of the heavy and light chains of anti-GD2 antibodies. These antibody constructs may be coupled to a label such as a radiolabel or to a protein such as streptavidin or pro-drug converting enzymes for use in imaging or therapeutic applications. The antibody constructs may also be transduced into T cells to produce populations of T cells which target GD2-producing tumor cells.

Abstract: Genetically-modified T cells with enhanced survival in vivo are obtained by transducing T cells with a recombinant polynucleotide encoding a fusion protein comprising a single chain Fv antibody (comprising the variable regions of the heavy and light chains of a selected antibody such as an anti-GD2 antibody) linked to CD28 receptor. T cells expressing this recombinant fusion protein exhibit enhanced survival when reintroduced to an in vivo environment.. These T cells can be used to induce an immune response to cells, particularly tumor cells, when express the antigen for which the antibody is specific. Cells expressing recombinant fusion proteins according to the invention can also be used for in vitro purging of stem cells/bone marrow and for in vivo targeting of tumor cells and other antigen-bearing cells for purposes of imaging.