The present invention concerns antigen binding proteins specifically binding melanoma associated antigen A (MAGE-A) protein-derived antigens. The invention in particular provides antigen binding proteins which specifically bind to the MAGE-A antigenic peptide comprising or consisting of SEQ ID NO: 1 in a complex with a major histocombatibility (MHC) protein. The antigen binding proteins of the invention contain, in particular, the complementary determining regions (CDRs) of novel engineered T cell receptors (TCRs) that specifically bind to said MAGE-A peptide/MHC complex. The antigen binding proteins of the invention are of use for the diagnosis, treatment and prevention of MAGE-A expressing cancerous diseases. Further provided are nucleic acids encoding the antigen binding proteins of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen binding proteins and pharmaceutical compositions comprising the antigen binding proteins of the invention.

In various aspects and embodiments, this disclosure provides methods for generating hematopoietic stem cells (HSCs), as well as compositions comprising the same, and methods of treating disease. The disclosure provides methods for preparing endothelial cells from pluripotent stem cells by expression (e.g., overexpression) of E26 transformation-specific variant 2 (ETV2) transcription factor. HSCs are then generated from the endothelial cells using mechanical, biochemical, pharmacological and/or genetic stimulation.

[Problems]

To provide a method for producing regenerated T cells via iPS cells into which TCRs isolated from tumor tissue-infiltrating CD106-positive T cells have been introduced.

[Solutions]

Provided is a method for producing regenerated T cells via iPS cells, comprising: 1. A step for preparing cDNAs respectively encoding a TCR chain and a TCR chain from individual cells in a CD106-positive T cell population obtained from subjects and having reactivity with a tumor-related antigen; 2. A step for reprogramming peripheral blood mononuclear cells which are obtained from the subjects and from which B cells and T cells have been removed or T cells into iPS cells, and selecting iPS cell clones having high efficiency of differentiation into T cells from the obtained iPS cells; 3. A step for introducing the cDNAs into the iPS cell clones, hematopoietic stem cells differentiated from the iPS cell clones, immature T cells differentiated from the hematopoietic stem cells, or mature T cells differentiated from the immature T cells; and 4. A step for performing the differentiation of the iPS cell clones having the cDNAs introduced therein, the hematopoietic stem cells or the immature T cells which have been obtained in step 3 into mature T cells and the proliferation of the mature T cells.

The invention discloses novel RAR gamma selective agonists used in the treatment of cancer. The invention also discloses administration of RAR gamma selective agonists to mammals, including humans for the purpose of selectively activating RAR gamma receptor and treat cancer by way of activating tumor infiltrating lymphocytes.

This invention relates generally to compositions and methods for modulating complement component 3 (C3) activity or expression to treat, control or otherwise influence tumors and tissues, including cells and cell types of the tumors and tissues, and malignant, microenvironmental, or immunologic states of the tumor cells and tissues. The invention also relates to methods of diagnosing, prognosing and/or staging of tumors, tissues and cells.

SIRP1alpha-41BBL fusion proteins are provided. Accordingly, there is provided a SIRPalpha-41BBL fusion protein comprising a single amino acid linker between the SIRPalpha and the 41BBL. Also there is provided a SIRPalpha-41BBL fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRP1alpha-41BBL fusion protein, host-cells expressing the SIRP1alpha-41BBL fusion protein and methods of use thereof.

Hematopoietic stem/progenitor cells (HSPC) and/or non-T effector cells are genetically modified to express (i) an extracellular component including a ligand binding domain that binds a cellular marker preferentially expressed on an unwanted cell; and (ii) an intracellular component comprising an effector domain. Among other uses, the modified cells can be administered to patients to target unwanted cancer cells without the need for immunological matching before administration.

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen, e.g., CD33 or EMR2, and a population of hematopoietic cells that are altered in the expression of the lineage-specific cell-surface antigen, e.g., CD33 or EMR2, for immunotherapy of hematological malignancies. Also disclosed herein are methods of administering an agent targeting more than one lineage-specific cell-surface antigen, and a population of hematopoietic cells that are altered in the expression of more than one lineage-specific cell-surface antigen, for immunotherapy of hematological malignancies. Cells comprising mutations in CD33, or EMR2, or more than one lineage-specific cell-surface antigen are also provided, as are methods of producing such cells using CRISPR-based base editor systems.

The present invention discloses humanized monoclonal antibodies that specifically bind to SLeA carbohydrate antigen with high specificity and selectivity, functional fragments of the humanized monoclonal antibodies such as scFv, and chimeric antigen receptors comprising the humanized monoclonal antibodies or the fragment thereof such as scFv. The invention further provides cells and compositions comprising the antibodies, fragments thereof or CARs as well as their use in diagnostics and treatment of cancer.

Peripheral blood mononuclear cells (PBMCs) can be used in place of DCs when pulsing with antigens, or antigen and adjuvant combination, and then administered to a subject as a vaccine to induce a protective immune response. The PBMC-based vaccine strategy provides a more marked and enduring protective immune response and is also capable of serving as a multi-organism prophylactic vaccine platform. The vaccine platform may be used to screen vaccine and adjuvant combinations and may also be used to allow for adjuvants that are otherwise unsafe for use in humans as the adjuvant may be removed prior to prophylactic administration of the pulsed PBMCs.