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: Intracellular delivery of a genetic construct to immune cells including: obtaining a deterministic mechanoporation (DMP) platform that includes a substrate having a surface and a plurality of capture sites, each said capture site having a boundary shape at the surface adapted and configured to support thereon a cell, and each said capture site having a bottom and including a sub-micron-scale projection extending from the bottom toward the surface of the substrate, wherein said projection is adapted and configured to penetrate a cell membrane and/or wall of the cell, and wherein the substrate has a plurality of aspiration vias situated at the bottom of the capture sites; introducing the cells to the surface in a liquid media; capturing the cells within the capture sites by applying a first hydrodynamic force; applying a second hydrodynamic force on the captured cell and locally rupturing the membrane and/or wall of the cell with the projection, introducing the genetic construct into the cells, and releasing th

Abstract: Chimeric antigen receptors for use in treating malignant melanoma and other cancers expressing CS1 are described.

Abstract: Chimeric antigen receptors targeted to IL-13Ra2 are described. The targeting domain is a IL13 variant having increased specificity for IL-13Ra2 relative to IL-13Ra1.

Abstract: Chimeric antigen receptors having a chlorotoxin domain and an IL-13 are described. These dual targeted chimeric antigen receptors are useful for treating glioblastoma and other cancers of neuroectodermal origin.

Abstract: Chimeric transmembrane immunoreceptors (CAR) targeted to PSCA are described.

Abstract: Immune cells, including T cells, expressing a chimeric antigen receptor targeted to CD45 are described. In some cases, the immune cells lack a functional CD45 gene. In some cases, the immune cells also include a modification (a suicide sequence) that allows the cells to be killed in vivo. The immune cells are useful for treating a variety of cancers.

Abstract: Methods for treating AL amyloidosis using chimeric antigen receptors targeting CS1 are described.

Abstract: Chimeric antigen receptors for use in treating malignant melanoma and other cancers expressing CS1 are described.

Abstract: Nucleic acid molecules that include a nucleotide sequence encoding a chimeric antigen receptor (CAR) and a nucleotide sequence encoding a protease sensitive scFv, wherein the chimeric antigen receptor comprises: an scFv targeting a tumor antigen, a spacer, a transmembrane domain, a co-stimulatory domain, and a CD3? signaling domain; and the protease-sensitive scFv and the scFv target the same tumor antigen are described.

Abstract: Chimeric antigen receptors that include an antigen recognition domain; a spacer domain derived from a modified immunoglobulin Fc region having one or more mutations in its CH2 region resulting in impaired binding to an FcR; and an intracellular signaling domain.

Abstract: Methods for preparing T cells or NK cells expressing a chimeric antigen receptor (CAR) is described. The methods entail: isolating a population of T cells, generating induced pluripotent stem cells (iPSCs) from the T cells, introducing a nucleic acid molecule encoding a CAR into the iPSCs to create CAR iPSCs; and differentiating the CAR iPSCs into CAR T cells or CAR NK cells.

Abstract: Chimeric transmembrane immunoreceptors (CAR) targeted to PSCA are described.

Abstract: Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain targeted to HER2, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

Abstract: Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain that includes chlorotoxin or a related toxin, or a variant of chlorotoxin or a related toxin, that binds to human glioma or other human tumor cells, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

Abstract: A method for manufacturing T cell populations enriched for cells expressing CD27 and useful in T cell therapy is described. The T cell populations are also useful for a variety of purposes requiring a highly active, long-lived T cell population. Such cells elicit a superior antitumor immune response in vitro and in vivo.

Abstract: Chimeric antigen receptors targeting both BAFF-R and CD19 are described as are methods for their use.

Abstract: Described are improved methods for treating solid tumors, such as malignant gliomas, with a dual approach utilizing a CAR-T immunotherapy and a viral oncolytic therapy.

Abstract: Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain that includes chlorotoxin or a related toxin, or a variant of chlorotoxin or a related toxin, that binds to human glioma or other human tumor cells, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

Abstract: T cells expressing a chimeric antigen receptor and a T cell receptor specific for CMV (bi-specific T cells) are described as a methods for using such cells in immunotherapy. In the immunotherapy methods, the recipient can be exposed to a CMV vaccine in order to expand and/or stimulate the be-specific T cells.