Aspects of the present invention relate to synthetic chromosomes that may be incorporated into leukocytes, wherein the synthetic chromosomes comprise nucleic acid sequences encoding multiple Chimeric Antigen Receptors (CARs). Such manipulated leukocytes can be used in medicine, notably in the treatment of a cancer such as in the treatment of cancer having solid tumors. The leukocytes may be lymphocytes, including tumor-infiltrating lymphocytes. T cells. NK cells or B cells. In a preferred aspect, the leucocytes are syngeneic and T cells.

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 present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

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.

The present invention relates to immune cells expressing chimeric antigen receptors against p95HER2 and bispecific antibodies for HER2 and CD3 and uses thereof in the treatment of cancer, in particular cancers which overexpress p95HER2.

Cancer therapy comprising both a population of genetically engineered T cells expressing a chimeric antigen receptor (CAR) and a population of antigen-presenting cells (APCs), which enhances efficacy of the CAR-expressing T cells.

The present invention belongs to the technical fields of immunology and oncologic therapies. Provided are a tumor microenvironment-regulated CAR-monocyte/macrophage, and a preparation method therefor and the use thereof. When the CAR-monocyte/macrophage forms a chimeric antigen receptor composite structure, GM-CSF can be expressed intracellularly and autocrine to extracellular to promote the differentiation of the CAR-monocyte/macrophage to form an M1 type macrophage, so that the tumor microenvironment can be further regulated while the property of resisting M2 type macrophage reversal in the tumor microenvironment is maintained, thereby sensitizing the anti-tumor effect of the CAR-monocyte/macrophage. On the basis of GM-CSF, a tumor microenvironment-regulated CAR macrophage technology platform is constructed, which can maintain the M1-type characteristics of CAR-M and can also produce a TME reversal effect, thereby achieving the efficient anti-tumor effect of a CAR-monocyte/macrophage.

In certain embodiments, this disclosure provides methods to generate DNA, RNA and/or DNA-peptide nanostructures based chimeric antigen receptor (CAR) T cell (engineered T cell) for cancer immunotherapy, and compositions made by these methods.

Compounds that either produced a higher proportion or greater absolute number of phenotypically identified nave, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.

Provided are natural killer cells engineered to express a chimeric antigen receptor (CAR) with Toll/interleukin-1 (IL-1) receptor (TIR) signaling domains, such as a Toll-like receptor (TLR) signaling domain or a IL-1 receptor (IL-1R) subfamily signaling domain. Further provided are compositions and methods for making and using such natural killer cells in immunotherapy for cancer. The CAR-NK cells may be CISH/iPSC-NK cells.