Provided are antibodies, fragments thereof, chimeric antigen receptors (CARs) and T cell receptors (TCRs) comprising one or more of the GPC3 binding domains disclosed herein. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

Provided are chimeric antigen receptors (CARs) comprising an NGK2D ecto domain. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

There is provided a chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—GY-AFSSS (SEQ ID No. 1); CDR2—YPGDED (SEQ ID No. 2) CDR3—SLLYGDYLDY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—SASSSVSYMH (SEQ ID No. 4); CDR2—DTSKLAS (SEQ ID No. 5) CDR3—QQWNINPLT (SEQ ID No. 6). There is also provided a cell comprising such a CAR, and the use of such a cell in the treatment of cancer, in particular a B cell malignancy.

Treatment and prevention of cancer using virus-specific immune cells, comprising a chimeric antigen receptor (CAR) or nucleic acid encoding a CAR, wherein the CAR comprises: (i) an antigen-binding domain which binds specifically to CD30, (ii) a transmembrane domain, and (iii) a signalling domain, wherein the signalling domain comprises: (a) an amino acid sequence derived from the intracellular domain of CD28, and (b) an amino acid sequence comprising an immunoreceptor tyrosine-based activation motif (ITAM), is disclosed.

One aspect according to the present disclosure relates to a novel nucleic acid ligand which is a new class of nucleic acid compound, the existence of which was considered impossible in the prior art. The novel nucleic acid ligand has specific binding affinity with respect to at least two different targets having three-dimensional structures, and the binding sites for the at least two targets are formed in or from a single nucleic acid ligand. The novel nucleic acid ligand according the present disclosure can simultaneously solve several problems of existing aptamers that the prior art could not solve. One aspect according to the present disclosure relates to a novel screening method for identifying the above-mentioned novel nucleic acid ligand. The novel screening method uses a step for sequentially contacting at least two different targets having three-dimensional structures to screen a novel nucleic acid ligand that was previously thought impossible.

The present invention relates to chimeric antigen receptor cells targeting ROBO1, in particular, enhanced CAR-T cells and CAR-NK cells targeting ROBO1, and preparation and application thereof. The cells can stably expressing CAR elements, while secreting extracellular domain molecules expressing PD-1 protein or mutants thereof, and thus may block PD-11PD-L1 molecular interaction. It has been found through animal experiments that the cells have very good anti-tumor effects, and the above-mentioned cells can significantly reduce tumor recurrence and improve the survival rate compared with the conventional ROBO1-targeted CAR modified cells.

The present invention relates to a chimeric molecule useful in adoptive cell therapy (ACT), and cells comprising the same. The chimeric molecule can act as a modulator of cellular activity enhancing responses when an endogenous T-cell receptor (TCR) is engaged with its cognate antigen. The present invention also provides proteins, nucleic acids encoding the chimeric molecule and therapeutic uses thereof.

The present invention relates to the field of manufacturing of Natural Killer (NK) Cells genetically modified with viral vectors carrying a polynucleotide coding for a Chimeric Antigen Receptors (CARs). The present invention further relates to CAR-NK cells obtained with the method and use of the CAR-NK cells in medicine, in particular for use in a method of treating cancer.

The present invention relates to an immune cell that are engineered to overexpress cell signaling pathway modulator(s) and a use thereof. As a specific example, an immune cell expressing a fusion protein comprising a chimeric antigen receptor and a cell signaling pathway modulator(s) performs an immune response by selecting a target cancer cell by a chimeric antigen receptor expressed on a cell membrane. In this case, the cell signaling pathway modulator is overexpressed in the cytoplasm, thereby being capable of regulating the activity of an immune cell. Therefore, the fusion protein comprising a chimeric antigen receptor and cell signaling pathway modulator(s), and the immune cell engineered to overexpress the cell signaling pathway modulator(s) of the present invention can be usefully used in the treatment of cancer.

Embodiments of the disclosure include methods and compositions for inhibiting the immune suppressive tumor microenvironment using cell therapy wherein the cells express a chimeric protein having an extracellular domain that binds TRAIL-R2 and an intracellular domain that in specific embodiments comprises one or more costimulatory domains that enhance activity of the cells upon activation. In specific embodiments, the chimeric protein comprises an scFv that targets TRAIL-R2 and an intracellular region that comprises a costimulatory domain from 4-1BB. In particular embodiments, the cells also express a therapeutic protein, such as a chimeric antigen receptor.