The present disclosure relates to methods for enhancing the efficiency of therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells, even when provided to a subject in sub-therapeutic amounts, are extremely effective in the treatment of cancer diseases, even those cancer diseases that are known to be difficult to treat with antigen receptor-engineered immune effector cells, such as solid tumors or cancers, if additionally target antigen for the antigen receptor is provided to the subject. Immune effector cells may be engineered ex vivo or in vitro and subsequently the immune effector cells may be administered to a subject in need of treatment, or immune effector cells may be engineered in vivo in a subject in need of treatment.

Embodiments of the disclosure include methods and compositions directed to targeting of cells that express the long form of Bone marrow stromal cell antigen 2 (BST2) protein, including cancer cells that express the long isoform of BST2. In particular embodiments, monoclonal antibodies or functionally active fragments thereof are utilized to target cells that express the long isoform of BST2. The monoclonal antibodies or functionally active fragments thereof may be utilized by themselves or as part of other entities, such as cells or engineered antigen receptors. The disclosure includes methods of treatment, prevention, and/or diagnosis using the encompassed antibodies or functional fragments thereof.

The invention relates to vaccines for breast cancer therapy. The invention also relates to methods of preventing and treating breast cancer using a breast cancer vaccine.

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: Z is a group of formula: (II) wherein P and Q are each independently CR.sub.12R.sub.13; or one of P and Q is NR.sub.14 and the other is CR.sub.12R.sub.13; the group X—Y is —NHSO.sub.2— or —SO2NH—; R.sub.1 is H, CN or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, Cl and alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, heteroaryl, SO.sub.2NR.sub.16R.sub.17, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; R.sub.9 is H or halo; and R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.16 and R.sub.17 are each independently H or alkyl; R.sub.15 is selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; and m and n are each independently 0, 1, 2 or 3. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

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Disclosed herein relates to immunotherapeutic polypeptides comprising neoepitopes, antigen presenting cells comprising the immunotherapeutic polypeptides, and a pharmaceutical composition comprising the immunotherapeutic polypeptides. Also disclosed herein is use of the immunotherapeutic polypeptides in treating a disease or condition.

The present disclosure provides in vitro modified cytotoxic T cells (CTLs) that comprise: a) a T-cell receptor (TCR) specific for a preselected antigen in a human; and b) a nucleic acid(s) encoding a chimeric antigen receptor (CAR) specific for a cancer-associated antigen. The present disclosure provides methods of producing the modified CTLs. The present disclosure provides of treating cancer, comprising administering the modified CTLs to an individual in need thereof.

Disclosed are compositions and methods for ex vivo expansion of tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT). Also disclosed are compositions and method for identifying an agent for ex vivo expansion of tumor-infiltrating lymphocytes for use in ACT. Also disclosed are methods for treating cancer using tumor-infiltrating lymphocytes expanded by the disclosed methods.

Contemplated compositions and methods generate a durable immune synapse and so lead to activated T-cells and memory T-cell formation by use of selected co-stimulatory receptors and their ligands in conjunction with selected neoepitopes. Moreover, immune competent cells are attracted into a tumor microenvironment after activation of the T-cells using hybrid or chimeric binding proteins that comprise a chemokine portion and that target components of necrotic cells.

Disclosed herein is a novel chimeric antigen receptor and use thereof. The novel chimeric antigen receptor consists of a signal peptide, an antigen binding domain, a transmembrane region, and an intracellular signal domain, and comprises a 4-1BB signal peptide and/or a 4-1BB molecular transmembrane region. Nucleic acid sequences of various chimeric antigen receptors are separated and purified and provided is a chimeric antigen receptor and a CAR-T cell which are specific for a CD19 malignant tumor antigen. In the malignant tumor killing test of hematological cell lines, the ability of immune cells to target and recognize tumor cells is significantly enhanced, and the killing activity against tumor cells is also enhanced.

Provided herein are methods and articles of manufacture for use with cell therapy for the treatment of diseases or conditions, e.g., cancer, including for predicting and treating a toxicity. In some embodiments, the toxicity is related to cytokine release syndrome (CRS). The methods generally involve assessing a change in a factor indicative of tumor burden prior to administration of a cell therapy in a subject that is associated with and/or correlate to a risk of developing toxicity. In some aspects, the methods can be used to determine if the subject is at risk or likely at risk for developing a toxicity following administration of the cell therapy. Also provided are methods for treating a subject having a disease or condition, in some cases involving administration of the cell therapy, based on assessment of risk of developing a toxicity following administration of the therapy. Also provided herein are reagents and kits for performing the methods.