Disclosed herein is a method for ex vivo expanding tumor-infiltrating lymphocytes for use in adoptive cell therapy (ACT). The method involves culturing tumor fragments from the subject in a culture medium containing IL-2 and a 41BB agonist in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and specificity. Also disclosed is a method for treating a tumor in a subject that involves treating the subject with nonmyeloablative lymphodepleting chemotherapy, and administering tumor-infiltrating lymphocytes expanded by the disclosed methods.

Methods of inhibiting metastasis in cancer patients are provided, wherein the methods comprise reducing TGF signaling, for example, by reducing TGF receptor II expression in myeloid cells. Vectors comprising a TGF receptor II RNAi nucleic acid sequence operably linked to a myeloid specific promoter also are provided. A method of diagnosing cancer in an individual by determining TGF receptor II expression in myeloid cells in the individual is provided. Additionally, a method of modulating TGF activity in myeloid cells in a cancer patient comprising administering a regulator of at least one of the GSK3 and PI3K pathways to the patient is provided.

Embodiments described herein relate to methods, devices, and computer systems thereof for the derivation of T CAR libraries (Universal Subject or Individual Subject) for personalized treatment of disease in a subject. In certain embodiments, differential screening of normal and diseased tissue expression data is utilized to determine disease-specific antigens and thereby generate T CAR cells reactive to such antigens to form a disease-specific library. In certain embodiments, determination of the most effective T CAR clones from the disease-specific library is based on the subject's own disease-specific antigens. In certain embodiments, a subject is treated with a therapeutically effective amount of T CAR clones.

Cancer treatment is provided, by irradiating an individual with a localized, high single dose or short course of doses at a primary tumor site; collecting T cells from the individual after a period of time sufficient activation of an anti-tumor response; treating the individual with an effective dose of dose of chemotherapy; and reintroducing the T cell population back to the individual.

The present invention relates to a method for identifying T-cell (or T-cell) receptors chains or parts thereof that mediate an anti-tumor or anti-infection response by identifying amino acid sequences comprising T-cells (or T-cell) receptors chains or parts thereof that are shared between different donors.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer, such as LIV1.sup.+ malignancies.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

In various aspects, the present disclosure provides polynucleotides encoding a fusion protein, as well as vectors, cells, and compositions comprising the same. In embodiments, the fusion protein includes an insulin signal peptide and an MDA-7/IL-24 protein. Methods of using the polynucleotides, vectors, cells, and compositions, such as in the treatment or prevention of cancer, are also provided.

The present invention provides methods for inducing and expanding anti-tumor immunity leading to enhanced clinical and immunotherapeutic responses. The invention also provides novel compositions and methods for the treatment of cancer.

The invention provides chimeric antigen receptor T (CAR-T) cell compositions for targeting tumor cells. The compositions contain (a) a CAR-T cell having in the extracellular domain of its CAR a catalytic antibody (e.g., a scFv molecule derived from catalytic antibody 38C2), and (b) an adapter compound containing a substrate moiety of the catalytic antibody that is linked to a targeting moiety that specifically recognizes a surface molecule of a target tumor cell. The compositions allow formation of a covalent bond between the catalytic antibody in the CAR and the targeting moiety. The targeting moieties employed in the compositions can be obtained via screening DNA-encoded compound library for specific binding to the target tumor surface molecules. Also provided in the invention are therapeutic methods of using the CAR-T cell compositions of the invention to in the treatment of various tumors of interest.