Abstract: Chimeric antigen receptors for use in treating lymphoma-associated C-C chemokine receptor type 4 (CCR4) and other cancers expressing CCR4 are described.

Abstract: A family of chimeric antigen receptors (CARs) containing a CD123 specific scFv was developed to target different epitopes on CD123. In some embodiments, such a CD123 chimeric antigen receptor (CD123CAR) gene includes an anti-CD123 scFv region fused in frame to a modified IgG4 hinge region comprising an S228P substitution, an L235E substitution, and optionally an N297Q substitution; a costimulatory signaling domain; and a T cell receptor (TCR) zeta chain signaling domain. When expressed in healthy donor T cells (CD4/CD8), the CD123CARs redirect T cell specificity and mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. Further, T cells obtained from patients with active AML can be modified to express CD123CAR genes and are able to lyse autologous AML blasts in vitro. Finally, a single dose of 5.0×106 CAR123 T cells results in significantly delayed leukemic progression in mice.

Abstract: In one embodiment, a gene expression signature for predicting risk of developing therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) after autologous hematopoietic cell transplantation (aHCT) is provided. In another embodiment, a method for predicting a risk for development of t-MDS/AML after aHCT is provided. Such a method may include providing a biological sample that contains CD34 cells from a subject; detecting a test expression level of a set of two or more genes of a gene expression signature; comparing the test expression level of a set of corresponding training expression levels that include a training case expression level and a training control expression level; and predicting a high risk of developing t-MDS/AML when the test expression level is at or about the training case expression level or predicting a low risk of developing t-MDS/AML when the test expression level is at or about the training control expression level.

Abstract: A family of chimeric antigen receptors (CARs) containing a CD123 specific scFv was developed to target different epitopes on CD123. In some embodiments, such a CD123 chimeric antigen receptor (CD123CAR) gene includes an anti-CD123 scFv region fused in frame to a modified IgG4 hinge region comprising an S228P substitution, an L235E substitution, and optionally an N297Q substitution; a costimulatory signaling domain; and a T cell receptor (TCR) zeta chain signaling domain. When expressed in healthy donor T cells (CD4/CD8), the CD123CARs redirect T cell specificity and mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. Further, T cells obtained from patients with active AML can be modified to express CD123CAR genes and are able to lyse autologous AML blasts in vitro. Finally, a single dose of 5.0×106 CAR123 T cells results in significantly delayed leukemic progression in mice.

Abstract: In one embodiment, a gene expression signature for predicting risk of developing therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) after autologous hematopoietic cell transplantation (aHCT) is provided. In another embodiment, a method for predicting a risk for development of t-MDS/AML after aHCT is provided. Such a method may include providing a biological sample that contains CD34 cells from a subject; detecting a test expression level of a set of two or more genes of a gene expression signature; comparing the test expression level of a set of corresponding training expression levels that include a training case expression level and a training control expression level; and predicting a high risk of developing t-MDS/AML when the test expression level is at or about the training case expression level or predicting a low risk of developing t-MDS/AML when the test expression level is at or about the training control expression level.

Abstract: According to the present invention there is provided a compound in the form of a transition metal compound including a transition metal, a phosphorus containing ligand, and a cyclic organic ligand. The phosphorus containing ligand is a heterocyclic organic compound with a ligating phosphorus atom which ligates with the transition metal, and which ligating phosphorus atom is an atom in the heterocyclic ring structure of the heterocyclic organic compound. The cyclic organic ligand is a cyclic organic compound with a ligating carbon atom in the cyclic ring structure of the cyclic organic compound which ligates with the transition metal by means of a double bound. The invention also relates to a method preparing such a compound and a metathesis reaction wherein such a compound is used as a catalyst.

Abstract: The present invention relates to a genetically engineered, CD19-specific chimeric T cell receptor and to immune cells expressing the chimeric receptor The present invention also relates to the use of such cells for cellular immunotherapy of CD9+ malignancies and for abrogating any untoward B cell function. The chimeric receptor is a single chain scFvFc:? receptor where scFvFc designates the extracellular domain, scFv designates the VH and VL chains of a single chain monoclonal antibody to CD19, Fc represents at least part of a constant region of an IgG1, and ? represents the intracellular signaling domain of the zeta chain of human CD3. The extracellular domain scFvFc and the intracellular domain ? are linked by a transmembrane domain such as the transmembrane domain of CD4. In one aspect, the chimeric receptor comprises amino acids 23-634 of SEQ I DNO:2.

Abstract: According to the present invention there is provided a compound in the form of a transition metal compound including a transition metal, a phosphorus containing ligand, and a cyclic organic ligand. The phosphorus containing ligand is a heterocyclic organic compound with a ligating phosphorus atom which ligates with the transition metal, and which ligating phosphorus atom is an atom in the heterocyclic ring structure of the heterocyclic organic compound. The cyclic organic ligand is a cyclic organic compound with a ligating carbon atom in the cyclic ring structure of the cyclic organic compound which ligates with the transition metal by means of a double bound. The invention also relates to a method preparing such a compound and a metathesis reaction wherein such a compound is used as a catalyst.

Abstract: The use of a phosphorus containing Ligand as a Ligand for a metathesis catalyst in a catalysed metathesis reaction wherein the phosphorus containing Ligand is a heterocyclic organic compound with a ligating phosphorus atom as an atom in the heterocyclic ring structure of the heterocyclic organic compound. The invention also relates to a metathesis catalyst such a phosphorus containing Ligand and to a metathesis reaction using the catalyst.

Abstract: Genetically engineered, CD19-specific redirected immune cells expressing a cell surface protein having an extracellular domain comprising a receptor which is specific for CD19, an intracellular signaling domain, and a transmembrane domain. Use of such cells for cellular immunotherapy of CD19+ malignancies and for abrogating any untoward B cell function. In one embodiment, the immune cell is a T cell and the cell surface protein is a single chain scFvFc:&zgr; receptor where scFv designates the VH and VL chains of a single chain monoclonal antibody to CD19, Fc represents at least part of a constant region of an IgG1, and &zgr; represents the intracellular signaling domain of the zeta chain of human CD3. The extracellular domain scFvFc and the intracellular domain &zgr; are linked by a transmembrane domain such as the transmembrane domain of CD4. A method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor.