The present invention relates to an oncolytic adenovirus capable of co-expressing interleukin-12 and a C-met-inhibiting oligonucleotide; and an antitumor immune-boosting composition and anticancer composition comprising the oncolytic adenovirus. The present invention has first identified an adenovirus system having simultaneous effects of IL-12 expression and C-met inhibition in cancer gene treatment. The adenovirus system of the present invention is capable of inhibiting C-met while expressing interleukin-12, thereby restoring immune functions in a tumor environment to enhance anticancer effects such as the inhibition of tumor recurrence and tumor growth and to inhibit tumor migration. Accordingly, the adenovirus system of the present invention can be effectively used in the treatment of cancer.

Novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have been identified herein in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides.

The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In some alternatives the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. In some alternatives, the ligand binding domains binds to CD171.

This disclosure relates to pharmaceutical formulations for multi-specific binding proteins having an epidermal growth factor receptor 2 (ErbB2 or HER2)-binding scFv, an NKG2D-binding Fab, and an antibody Fc domain. Also provided are dosage regimens for such multi-specific binding proteins and pharmaceutical formulations for use in treating cancer, such as locally advanced or metastatic solid tumor.

Disclosed herein are polypeptide fragments and polynucleotides based on mutant capicua transcriptional repressor (CIC), catenin beta 1 (CTNNB1), v-erb-b2 erythroblastic leukemia viral oncogene homolog B (ERBB2), kirsten rat sarcoma (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), splicing factor 3b subunit 1 (SF3B1), SRY-box transcription factor 17 (SOX17), tumor protein 53 (TP53), and cytomegalovirus (CMV) sequences, vectors, host cells, viruses, methods for generating CD8+ T-cells, and methods of treatment. Also disclosed herein are T-cell receptors (TCRs), polynucleotides, vectors and cells comprising the TCRs, and methods of treatment.

Breast cancer is a leading cancer diagnosed in women in the U.S. and globally. To combat this deadly disease, continued innovation in immunotherapy treatment methods as an alternative to chemotherapies is gaining traction with promising results. Immunotherapy is the use of medicines to stimulate a subject's own immune system to recognize and destroy cancer cells more effectively. The instant application discloses an immunotherapy treatment and treatment method for breast cancer tumors with Her-2/neu overexpression.

Chimeric proteins or chimeric protein complexes, such as an Fc-based chimeric protein complexes directed to FMS-like tyrosine kinase 3 (FLT3), optionally composed of a FMS-like tyrosine kinase 3L (FLT3L) domain and human cytokines, which find use in, e.g., cancer treatments, are described.

The present disclosure provides methods of treating cancer in a patient determined to have an HER2 exon 21 mutation by administering a third-generation tyrosine kinase inhibitor, such as poziotinib.

The present disclosure provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, e.g., acute myeloid leukemia (AML) and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.

Provided are various embodiments relating to TrkA ECD polypeptides from companion animal species that bind to NGF. Such polypeptides can be used in methods to treat NGF-induced condition related to chronic pain and/or inflammatory pain in companion animals, such as canines, felines, and equines.