13 results about "Hematologic cancer" patented technology

This invention describes CD33 antibodies and their antigen-binding fragments, as well as CD33 / vδ2 multispecific antibodies or their antigen-binding fragments. The invention also describes polynucleotides encoding these antibodies, compositions comprising these antibodies, methods for producing these antibodies, and methods for treating or preventing diseases such as hematological cancers using these antibodies.

A single domain antibody having binding specificity for the human GPRC5D protein is provided. Such antibodies, and multispecific counterparts and chimeric antigen receptors thereof, are capable of targeting cancer cells expressing GPRC5D, and thus are useful in the treatment of cancer, particularly hematologic cancer.

The present disclosure relates to novel nucleic acids for immune cell adapters, comprising a ribonucleic acid of formula I: R1-SP-R2-R3-R4-R5 (I) wherein R1 is a 5'non-transcriptional region (UTR); sP encodes a signal peptide; r2 encodes a first single chain variable fragment (scFv) that binds to a first extracellular protein or a heavy chain variable region (VH only) that binds to a first extracellular protein; r3 encodes a second scFv that binds to a second extracellular protein; r4 encodes a half-life extender; r < 5 > is 3 'UTR wherein R < 1 > to R < 5 > are in the 5' to 3 'direction for use in the treatment of cancer, including but not limited to hematological cancers, including multiple myeloma.

Disclosed are compositions and methods for targeted treatment of cancer, such as hematologic cancer. In particular, chimeric antigen receptor (CAR) T cells are disclosed that can be used with adoptive cell transfer to target and kill cancer cells with reduced antigen escape. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with hematologic cancer that involves adoptive transfer of the disclosed CAR T cells.

This invention discloses 6-substituted 2-([1,1'-biphenyl]-4-yl)quinoline-4-carboxylic acid analogs, which are inhibitors of dihydroorotate dehydrogenase (DHODH) with improved pharmacokinetic properties. The disclosed compounds can be used to treat a variety of disorders and diseases where inhibition of DHODH may be clinically useful, including cancers such as hematologic cancers, including acute myeloid leukemia (AML), graft-versus-host disease, autoimmune disorders, and disorders associated with T-cell proliferation. When administered orally, the disclosed compounds exhibit flipped kinetics, i.e., pharmacokinetics in which the absorption rate, rather than the elimination rate, dominates the pharmacokinetic profile. The disclosed compounds exhibit sustained pharmacokinetic characteristics rather than immediate release characteristics. This summary is intended as a scanning tool for searching in a specific field and is not intended to limit this disclosure.

PI3Kδ implicates hematologic cancers and solid tumors. Alternative splicing is a post-transcriptional process for acquiring proteomic diversity in eukaryotic cells. Emerging evidence highlights the involvement of aberrant mRNA splicing in cancer development / progression. PI3Kδ-L and PI3Kδ-S are overexpressed in advanced solid tumors, such as prostate, breast, colon, lung and pancreatic cancers. Differential PI3Kδ and PI3Kδ-S expression profiles were identified in a panel of solid tumor cells. PI3Kδ inhibitor Idelalisib and SRPK1 / 2 inhibitor SRPIN340 were employed to assess their efficacies on inhibiting the PI3Kδ-expressing solid tumors. Idelalisib effectively inhibits PI3Kδ-L and its downstream signaling. Idelalisib fails to inhibit PI3Kδ-S activity and its downstream signaling. SRPIN340 reverses the aberrant mRNA splicing, thereby inhibiting the downstream AKT / mTOR signaling. In vitro functional assays further demonstrate that a combination of Idelalisib and SRPIN340 achieve a synergistic drug effect, with drastically reduced cell viabilities / growths of tumor spheroids, in inhibiting the advanced tumor cells.

Methods are provided for the continuous administration to a subject requiring treatment of a formulation comprising an immunomodulatory imide compound. In some modalities, the method is used for the treatment of multiple myeloma, transfusion-dependent anemia due to low- or intermediate-risk myelodysplastic syndromes, mantle cell lymphoma, hematologic cancers, or solid tumor cancers.

Stapled BAD BH3 peptides and compositions comprising the same that are useful in overcoming venetoclax resistance are provided. Also provided are methods of using the stapled BAD BH3 peptides for treating a BCL-2 expressing and / or dependent cancer (e.g., a hematologic cancer or a solid tumor) in a human subject in need thereof. In some cases, the cancer is a venetoclax-resistant cancer due to acquired mutations in the BCL-2 protein. The methods involve administering to the human subject a stapled BAD BH3 peptide or pharmaceutical composition or delivery vehicle comprising the stapled BAD BH3 peptide disclosed herein.

The present disclosure provides a chimeric antigen receptor (CAR) immunotherapy for treating a hematologic cancer comprising (a) genetically modifying a population of immune effector cells comprising T cell receptors (TCRs) to stably express at least one CAR, wherein the ectodomain of the CAR specifically binds a cancer antigen; (b) expanding the population of CAR-containing immune effector cells in the presence of one or more cytokines in vitro to achieve a therapeutic dose, wherein the population of CAR-containing immune effector cells exhibits a nonexhausted memory T cell phenotype; and (c) infusing eligible subjects with the CAR-containing immune effector memory T cell phenotype population of cells as needed until the hematologic cancer in the body is destroyed. The intracellular signal transduction domain of the CAR includes 4-1BB, a CD3zeta T cell activation chain and a genetically engineered 'TLE3, which can be ectopically expressed.

A method of treating hematological cancer comprising administering to a patient in need thereof a therapeutically effective amount of a phosphatidylinositol 3-kinase gamma (PI3Kg) inhibitor and an antimetabolite, optionally a therapeutically effective amount of a BCL-2 inhibitor. A method of identifying hematological cancer patients susceptible to treatment with a PI3Kg inhibitor. A method of treating hematological cancer, the method comprising administering to a patient in need thereof a therapeutically effective amount of a p-21 activated kinase 1 (PAK-1) inhibitor, optionally a therapeutically effective amount of a BCL-2 inhibitor.

The present disclosure relates to methods of treating hematological cancers, including resistant forms thereof. Also provided are methods of treating aberrantly activated (or reactive) matrices, such as cancer matrices associated with blood system cancers, to alter their state, e.g., to make it / their tolerance to cancer cells low, and / or to reduce the resistance of matrices to treatment with antibodies or antigen-binding fragments thereof, which are inhibitors of the FBG region of tenascin C.

The present disclosure relates generally to compositions and methods for improving the safety of adoptive immune cell therapy, including the use of a depletion tag (e.g., an epitope or a mimotope) that is capable of binding to another molecule (e.g., an antibody) to facilitate the depletion of the engineered immune cells. One class of depletion tags disclosed herein contain an epitope or mimotope derived from a biomarker of a hematologic cancer (e.g., CCR4). A second class of depletion tags disclosed herein contain an epitope or mimotope derived from the same antigen that the engineered receptor binds to (e.g., a DLL3 derived depletion tag for engineered immune cells that bind to DLL3).

The present application provides compositions and methods for producing antigen presenting cells (APCs) from cancer cells (e.g., hematologic cancer cells), the present invention relates to one or more agents selected from the group consisting of: a STAT3 activator (e.g., IL-10), an IFN [gamma] receptor activator (e.g., IFN [gamma]), a TNF [alpha] receptor activator (e.g., TNF [alpha]), an IL-4 receptor activator (e.g., IL-4), a GM-CSF receptor activator (e.g., GM-CSF), and / or an IL-6 receptor activator (e.g., IL-6). Also provided are APCs thus produced, as well as methods of activating immune cells (e.g., T cells) via co-culture with APCs. Also provided are activated immune cell compositions and methods of treatment involving activated immune cells.