Abstract: The presently disclosed subject matter provides antigen-binding proteins (e.g., chimeric antigen receptors) and antibodies or antigen-binding portions thereof that bind to a Foxp3 peptide/MHC molecule complex. Such antibodies, fusion proteins and conjugates thereof are useful for inhibiting regulatory T cells and treating cancers.

Abstract: The present invention provides soluble single wall nanotube (SWNT) constructs functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereto. The targeting moiety and the payload molecules may be attached to the soluble SWNT via a DNA or other oligomer platform attached to the SWNT. These soluble SWNT constructs may comprise a radionuclide or contrast agent and as such are effective as diagnostic and therapeutic agents. Methods provided herein are to diagnosing or locating a cancer, treating a cancer, eliciting an immune response against a cancer or delivering an anticancer drug in situ via an enzymatic nanofactory using the soluble SWNT constructs.

Abstract: This invention provides peptides, immunogenic compositions and vaccines comprising same, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising same.

Abstract: The present invention provides new and improved methods for screening for and/or identifying T cell epitopes, as well as various assays and compositions (such as nucleic acid molecules, vectors, viruses, peptides, libraries, and cells), that are useful in carrying out such methods. Such methods and compositions can be used to predict and/or study the toxicity and off-target effects of T-cells, TCRs, or TCR-like molecules.

Abstract: The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

Abstract: Disclosed herein is a bi-specific form of a T cell receptor mimic (TCRm) mAb with reactivity to human immune effector cell antigen and a WT1 peptide/HLA-A epitope. This antibody selectively bound to leukemias and solid tumor cells expressing WT1 and HLA-A as well as activated resting human T cells to release interferon-(IFN-?) and to kill the target cancer cells in vitro. Importantly, the antibody mediated autologous T cell proliferation and directed potent cytotoxicity against fresh ovarian cancer cells. Therapeutic activity in vivo of the antibody was demonstrated in NOD SCID SCID Yc*(NSG) mice with three different human cancers expressing WT1/HLA-A2 including disseminated Ph+ acute lymphocytic leukemia (ALL), disseminated acute myeloid leukemia, and peritoneal mesothelioma. In both of the leukemia xenograft models, mice that received the antibody and T cells also showed longer survival and delayed limb paralysis.

Abstract: Provided herein are methods of modulating immune response, including methods of treating a cancer or an infection using a combination of kinase modulators and immunotherapy that promotes immune response. Also provided herein are methods of treating an autoimmune disease or graft-versus-host disease, and methods of reducing the risk of solid organ transplant rejection using a combination of kinase modulators and immunosuppressive therapy.

Abstract: This invention provides WT1 peptides and methods of treating, reducing the incidence of, and inducing immune responses against a WT1-expressing cancer, comprising same.

Abstract: This invention provides methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, by administering a combination of at least one WT1 peptide, or cytotoxic T cells (CTLs) against a WT1-expressing cancer, and at least one checkpoint inhibitor. The at least one WT1 peptide can be administered to the subject by administering one or more agents to the subject resulting in delivery of one or more WT1 peptides and induction of an immune response against the WT1-expressing cancer. Examples of these WT1 delivery agents include: (i) an isolated WT1 peptide, (ii) a nucleic acid encoding the at least one WT1 peptide, and (iii) an immune cell comprising or presenting the at least one WT1 peptide or nucleic acid encoding the at least one WT1 peptide.

Abstract: Provided herein is the two component self-assembly single wall nanotube system and the single wall nanotube construct that is the second component.

Abstract: The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

Abstract: This invention provides peptides, immunogenic compositions and vaccines, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising heteroclitic peptides derived from the WT-1 protein.

Abstract: The presently disclosed subject matter provides antigen-binding proteins that specifically bind to Preferentially expressed antigen of melanoma (PRAME), including humanized, chimeric and fully human antibodies against PRAME, antibody fragments (e.g., scFv, Fab and F(ab)2), chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen-binding proteins and antibodies bind to a PRAME peptide/HLA class I molecule complex. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of PRAME associated diseases, including for example, breast cancer, ovarian cancer, melanoma, lung cancer, gastrointestinal cancer, brain tumor, head and neck cancer, renal cancer, myeloma, neuroblastoma, mantle cell lymphoma, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML), Non-Hodgkin lymphoma (NHL), and Chronic lymphocytic leukemia (CLL).

Abstract: Provided herein are methods for delivering a molecule in situ to a cell and for treating a cancer via the in situ delivery. The methods comprise contacting or administering to the cell, as two separate components, a morpholino oligonucleotide comprising a targeting moiety followed by a single wall nanotube construct comprising second morpholino oligonucleotides complementary to the first morpholino oligonucleotides and one or both of a therapeutic or diagnostic payload molecule linked to the single wall nanotube construct. Upon self-assembly of a single wall nanotube complex via hybridization of the first morpholino and second complementary morpholino oligonucleotides at the cell, the payload molecule is delivered. Also provided is the two component self-assembly single wall nanotube system and the single wall nanotube construct comprising the second component.

Abstract: Antigen binding proteins specific for an HLA-A2 restricted Ras peptide are disclosed. The antigen binding proteins encompass antibodies in a variety of forms, including full-length antibodies, substantially intact antibodies, Fab fragments, F(ab?)2 fragments, and single chain Fv fragments. Fusion proteins, such as scFv fusions with immunoglobulin or T-cell receptor domains, and bispecific antibodies incorporating the specificity of the antigen binding region for each peptide are also contemplated by the disclosure. Furthermore, immunoconjugates may include antibodies to which is linked a radioisotope, fluorescent or other detectable marker, cytotoxin, or other molecule are also encompassed by the disclosure. Among other things, immunoconjugates can be used for delivery of an agent to elicit a therapeutic effect or to facilitate an immune effector function.

Abstract: This invention provides peptides, immunogenic compositions and vaccines, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising heteroclitic peptides derived from the WT-1 protein.

Abstract: Functionalized single walled or multi-walled carbon nanotubes (f-CNTs) can be delivered into mammals to targeted organs, such as the kidney and the liver. These f-CNTs may be non-covalently linked or covalently linked to therapeutic agents. In particular, the application delivers carbon nanotube-therapeutic agent conjugates to a target organ, thereby preventing or reducing damages to the organ caused by other agents or procedure.

Abstract: The present invention provides soluble single wall nanotube (SWNT) constructs functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereto. The targeting moiety and the payload molecules may be attached to the soluble SWNT via a DNA or other oligomer platform attached to the SWNT. These soluble SWNT constructs may comprise a radionuclide or contrast agent and as such are effective as diagnostic and therapeutic agents. Methods provided herein are to diagnosing or locating a cancer, treating a cancer, eliciting an immune response against a cancer or delivering an anticancer drug in situ via an enzymatic nanofactory using the soluble SWNT constructs.

Abstract: Provided herein is a one-step method for chelating actinium-225 to a construct comprising a chelator linked to a bio-molecule, such as, an antibody or monoclonal antibody, via a bifunctional ligand in, for example, a 3-arm configuration. Also provided are methods for increasing the radiochemical yield of an actinium-225-chelant-biomolecule complex and for producing a high specific activity actinium-225 complex. The chelation is performed at a physiological temperature, about 37° C. Also provided are high specific activity actinium-225 complexes, that is, actinium-225 chelated to the chelator-biomolecule construct and pharmaceutical compositions thereof. Further provided are methods of treating a neoplastic disease or disorder with the actinium-225 complexes.

Abstract: The present invention provides soluble single wall nanotube (SWNT) constructs functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereto. The targeting moiety and the payload molecules may be attached to the soluble SWNT via a DNA or other oligomer platform attached to the SWNT. These soluble SWNT constructs may comprise a radionuclide or contrast agent and as such are effective as diagnostic and therapeutic agents. Methods provided herein are to diagnosing or locating a cancer, treating a cancer, eliciting an immune response against a cancer or delivering an anticancer drug in situ via an enzymatic nanofactory using the soluble SWNT constructs.