Methods of culturing T cells are provided. Accordingly there is provided a method of culturing T cells comprising culturing T cells in the presence of a T cell stimulator, an exogenous CCL21 and an exogenous ICAM1, thereby culturing the T cells. Also provided are cell cultures, isolated T cells and uses of same.

An immunoresponsive cell, such as a T-cell expressing (i) a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and (ii) a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and g) a binding element that specifically interacts with a second epitope on a target antigen.

This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

The current invention provides monocytic cells transfected with chimeric antigen receptor (CAR) to selectively home to tumors and upon homing differentiate into dendritic cells capable of activating immunity which is inhibitory to said tumor. In one embodiment of the invention, monocytic cells are transfected with a construct encoding an antigen binding domain, a transcellular or structural domain, and an intracellular signaling domain. In one specific aspect of the invention, the antigen binding domain interacts with sufficient affinity to a tumor antigen, capable of triggering said intracellular domain to induce an activation signal to induce monocyte differentiation into DC.

The current invention provides monocytic cells transfected with chimeric antigen receptor (CAR) to selectively home to tumors and upon homing differentiate into dendritic cells capable of activating immunity which is inhibitory to said tumor. In one embodiment of the invention, monocytic cells are transfected with a construct encoding an antigen binding domain, a transcellular or structural domain, and an intracellular signaling domain. In one specific aspect of the invention, the antigen binding domain interacts with sufficient affinity to a tumor antigen, capable of triggering said intracellular domain to induce an activation signal to induce monocyte differentiation into DC.

A bispecific cytotoxic lymphocyte or macrophage-redirecting autoantibody comprising a cytotoxic lymphocyte or macrophage targeting domain and an autoantibody. Methods for producing bispecific cytotoxic lymphocyte or macrophage-redirecting autoantibody comprising a cytotoxic lymphocyte or macrophage targeting domain and an autoantibody. Methods for treating a subject in need thereof comprising administering to the subject an isolated bispecific cytotoxic lymphocyte or macrophage-redirecting autoantibody.

The present disclosure provides an automated method of producing genetically modified immune cells, including chimeric antigen receptor T (CAR T) cells, utilizing a fully-enclosed cell engineering system.

Provided methods of obtaining a plurality of T cell receptors specifically recognizing a target tumor antigen peptide from an individual that has clinically benefitted from an immunotherapy, such as Multiple Antigen Specific Cell Therapy. Also provided tumor-specific TCRs, engineered immune cells expressing the TCRs and methods of treating a disease using the engineered immune cells.

Disclosed are compositions and methods comprising the administration of pulsed dendritic cells and an immunoregulator molecule inhibitor for the treatment of cancer.

The present disclosure concerns combination therapy for cancer that utilizes (i) an oncolytic virus; (ii) a virus comprising nucleic acid encoding an immunomodulatory factor; and (iii) at least one cell comprising a chimeric antigen receptor (CAR) specific for a cancer cell antigen. In particular embodiments, the virus comprises nucleic acid encoding an immunomodulatory factor comprises nucleic acid encoding IL-12 and/or antagonist anti-PD-L1 antibody.

Described herein are methods for assessing activity of engineered cells, such as engineered immune cells by using non-cellular substrates. Also described herein are methods for determining suitability of the engineered cells for treatment (e.g., via administration of the engineered cells) of a subject in need thereof.