Described herein are methods of selecting a treatment for, and optionally treating, a subject who has a tumor and methods for determining is a subject who has a tumor is likely to benefit from an immunotherapy treatment. The methods disclosed herein can include the use of a long non-coding RNA, and/or a ribonucleoprotein, as biomarkers of patient response to immunotherapy treatment, such as an immune checkpoint inhibitor.

Provided herein are compositions, methods, and uses involving bispecific binding molecules that specifically bind to HER2, a receptor tyrosine kinase, and to CD3, a T cell receptor, and mediate T cell cytotoxicity for managing and treating disorders, such as cancer. Also provided herein are uses and methods for managing and treating HER2-related cancers.

Herein are provided anti-EGFR single domain antibodies (sdAb) prepared by immunizing a llama with recombinant human EGFRvIII. VHH antibodies specific to EGFR were isolated. The example antibodies initially produced comprise CDR1, CDR2, and CDR3 sequences corresponding, respectively to SEQ NOs: 1-3, 4-6, 7-9, 10-12, 13-15, 16-18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39, 40-42, 43-45, and 46-48; and related sequences, including humanized variants. Also provided are multivalent antibodies comprising any one of the sdAbs, including bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and trispecific killer cell engagers (TriKEs). Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the aforementioned sdAbs. Uses of these molecules in the treatment of cancer are also described, in particularly EGFR-high cancers. Hinge lengths may be selected to achieve desired activities, such as high activity or high selectivity for target vs. non-target cells.

T cells expressing a chimeric antigen receptor and a T cell receptor specific for CMV (bi-specific T cells) are described as a methods for using such cells in immunotherapy. In the immunotherapy methods, the recipient can be exposed to a CMV vaccine in order to expand and/or stimulate the be-specific T cells.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells wherein the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment, and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells wherein the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment, and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

The present invention generally relates to T-cells, such as CD8+ T-cells, CD4+ T-cells, CD3+ T-cells, T-cells or natural killer (NK) T-cells, transfected/transduced with a fusion protein which is recruited by the use of trivalent, bispecific antibody molecule which specifically binds to/interacts with the extracellular domain of the fusion protein. More precisely, the present invention relates to a kit comprising the nucleic acid molecules, vectors and/or the fusion proteins of the present invention and the trivalent, bispecific antibody molecules of the present invention. Further aspects of the inventions are expression vectors comprising nucleic acid molecules encoding the fusion proteins as well as the trivalent, bispecific antibody molecules. Further, a process for the production of the trivalent, bispecific antibody molecules of the invention and a medicament/pharmaceutical composition comprising said trivalent, bispecific antibody molecules are described. The invention also provides the use of said trivalent, bispecific antibody molecules in a method for the treatment of particular diseases as well as a pharmaceutical compositions/medicament comprising said trivalent, bispecific antibody molecules, wherein said trivalent, bispecific antibody molecule(s) is (are) to be administered in combination with transduced T-cells comprising the fusion protein of the invention. The invention also provides a method for the treatment of particular diseases.

The present invention relates to an artificially manipulated immune system having an improved immune effect. More particularly, the present invention relates to an immune system having functions artificially altered which comprises artificially manipulated immunoregulatory elements and cells containing the same. Contemplated according to a particular embodiment is an immune system comprising artificially manipulated immunoregulatory genes such as PD-1, CTLA-4, A20, DGK, DGK, FAS, EGR2, PPP2R2D, PSGL-1, KDM6A, and TET2, and/or expression products thereof.

Methods for preparing T cell populations useful for a variety of purposes requiring a highly active, long-lived T cell population. The T cell populations are enriched for: nave T cells (TN), memory stem cells (TSCM) and central memory T cells (TCM). These cell populations can be derived from peripheral blood mononuclear cells (PBMC) by both: 1) depleting unwanted cell populations such as CD14 expressing myeloid cells and CD25 expressing cells; and 2) enriching for CD62L expressing memory and nave T cells.