Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b)a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.

An aspect of the invention provides nucleic acids comprising a nucleotide sequence encoding chimeric antigen receptor (CAR) amino acid constructs. Polypeptides, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CAR constructs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Provided herein are multi-functional chimeric antigen receptor (CAR)-based compositions and their use in directing immune responses to target cells. The compositions have uses that include treating hyperproliferative disorders such as cancer. The provided methods generally include the use of a CAR cell in combination with an Adapter. The Adapter confers the ability to modulate, alter, and/or redirect CAR cell-mediated immune response in vitro and in vivo. In some embodiments, the CAR cell comprises a genetic modification to reduce or eliminate the expression of a targeted antigenic determinant.

The present invention provides CD160 binding domains. The invention also relates to antibodies or fragments thereof, chimeric antigen receptors (CARs) and bi-specific T cell engagers (BiTEs) which comprise such binding domains.

A target protein for viral vector-based anticancer therapy, and a binding molecule or a fragment thereof which specifically binds thereto are disclosed. A conformational epitope of protein A56, and a binding molecule or a fragment thereof which specifically binds thereto are disclosed. The A56-binding molecule or a fragment thereof, which binds to a conformational epitope of A56 forms a specific structural bond with A56 and shows high affinity thereto. Administering a vaccinia virus-based oncolytic virus, A56 is expressed on the cancer cell surface in various carcinomas. The A56-binding molecule or a fragment thereof effectively targets A56 that is specifically expressed on the cancer cell surface, which enables targeted therapy for cancer cells that have survived even infection with an oncolytic virus, thereby providing effective anticancer therapy.

Embodiments relate to a modified T cell comprising an antigen binding molecule, wherein expression and/or function of CDC42 in the modified cell has been enhanced. In embodiments, the modified cell has an increased level of cytokine release in response to an antigen that the antigen binding molecule binds as compared to a corresponding T cell that does not overexpress CDC42. In embodiments, the cytokine release comprises a cytokine release of IFN?. In embodiments, the modified cell has an enhanced migration capability in response to a chemokine as compared to a corresponding T cell that does not overexpress CDC42.

The present invention provides compositions and methods for regulating the specificity and activity of immune effector cells for use in immunotherapy. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a NKR-CAR which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

Provided herein are immune cells and methods of use, wherein the immune cells include a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular antigen binding domain that binds specifically to a first epitope; and an inhibitory chimeric antigen receptor (iCAR), wherein the iCAR comprises an extracellular antigen binding domain that binds specifically to a second epitope, wherein the immune cell is activated when the immune cells binds to the first epitope and does not bind to the second epitope; and wherein the immune cell is inactivated when the immune cell binds to the first and second epitopes.

Provided herein are methods for expedited manufacturing of engineered lymphocytes which are demonstrated to be associated with a favorable complete response rate and overall survival, and reduced risk of prolonged thrombocytopenia. The expedited manufacturing process can prepare transduced lymphocytes having improved efficacy or reduced adverse effects in treating cancer. An example process includes acquiring lymphocytes from a patient through apheresis, incubating the lymphocytes with a polynucleotide vector to transduce the lymphocytes to produce transduced lymphocytes, culturing the transduced lymphocytes, and infusing the transduced lymphocytes to the patient predicting a likelihood of a complete response, an overall survival rate, and a risk of prolonged thrombocytopenia in a subject receiving an immunotherapy.

The invention provides a recombinant chimeric antigen receptor (CAR) gene, a vector containing the same, a CAR-T cell and a use thereof. The recombinant CAR gene comprises a nucleic acid sequence encoding an antigen-binding portion of a CD30 antibody, a transmembrane portion and a CD137 cytoplasmic functional region and a CD3zeta cytoplasmic functional region linked in any order; also provides a method of treating Hodgkin's lymphoma or anaplastic large cell lymphoma or other CD30-positive tumors using the CAR-T cells of the invention.