The disclosure provides antibody molecules that bind to TCR V? regions and multispecific molecules comprising said antibody molecules. Additionally, disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, pharmaceutical compositions comprising aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

The present invention provides a universal, yet adaptable, anti-tag chimeric antigen receptor (AT-CAR) system which provides T cells with the ability and specificity to recognize and kill target cells, such as tumor cells, that have been marked by tagged antibodies. As an example, ?FITC-CAR-expressing T cells have been developed that specifically recognize various human cancer cells when those cells are bound by cancer-reactive FITC-labeled antibodies. The activation of ?FITC-CAR-expressing T cells is shown to induce efficient target lysis, T cell proliferation, and cytokine/chemokine production. The system can be used to treating subjects having cancer.

Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

Provided herein are T-cell receptor (TCR) fusion proteins (TFPs). T-cells engineered to express one or more TFPs. and methods of use thereof for the treatment of diseases, including cancer.

The present invention provides methods for expanding TILs and producing therapeutic populations of TILs. According to exemplary embodiments, at least a portion of the therapeutic population of TILs are gene-edited to enhance their therapeutic effect. According to further embodiments, methods for gene-editing TILs include intratumoral delivery of expression vectors for immune checkpoint inhibitors using an electroporation system prior to harvesting the tumor for TIL production. According to yet further embodiments, an adjuvant therapy for cancer includes delivery of expression vectors for immune checkpoint inhibitors before, after or before and after infusion of TILs for treating cancer.

The present disclosure provides orthogonal chimeric cytokine receptor/orthogonal cytokine pairs and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising an orthogonal chimeric cytokine receptor (e.g., an oIL2R-IL9R chimeric receptor) and a chimeric antigen receptor (CAR) or a T cell receptor (TCR). The present disclosure further provides an oncolytic adenoviral vector comprising a nucleic acid sequence encoding an orthogonal cytokine (e.g., oIL2), as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof.

The disclosure features amphiphilic ligand conjugates including a peptide or a ligand for a mucosal-associated invariant T-cell and a lipid and T cell receptor modified immune cells. The disclosure also features compositions and methods of using the same, for example, to stimulate proliferation of T cell receptor expressing cells.

Described herein is a recombinant Eomes protein that restores the cytotoxic activity of exhausted immune cells. This protein comprises, a nuclear localization sequence (NLS), the transcription factor associated domain of Eomesodermin (Eomes), and a protein-transduction domain (PTD). The NLS-Eomes-PTD polypeptide spontaneously internalizes into NK cells and travels to the nucleus to control the transcription of its down-stream signaling pathways. Introduction of the NLS-Eomes-PTD polypeptide into ExNK cells (i) decreases the expression of an inhibitory antigen on ExNK cells; (ii) increases cytolytic activity: (iii) enhances cytokine secretion; (iv) improves proliferation; and (v) inhibits tumor growth.

Provided herein are anti-CD72 nanobodies and methods of using such nanobodies for diagnostic and therapeutic purposes.

Provided are methods and articles of manufacture for use with cell therapy for the treatment of diseases or conditions, e.g., cancer, including for predicting likelihood of the subject responding to a therapy, such as a cell therapy, e.g., a chimeric antigen receptor (CAR) T cell therapy. In some aspects, the predicting is based on detecting certain biomarkers of immune cells associated with and/or that correlate with response following administration of the therapy. The methods generally involve detecting a marker by assaying a biological sample from a subject that is a candidate for treatment, optionally with a cell therapy, to determine if the subject is likely to respond to the therapy. The present disclosure also provides methods for treating a subject having a disease or condition, in some cases involving administration of the cell therapy, based on assessment the biomarker. Also provided herein are reagents and kits for performing the methods.