The present invention relates to low affinity dual chimeric antigen receptors (CARs), which provide cytotoxicity against heterogenous tumors and alleviate on-target, off-tumor toxicities. The dual CARs are constructed to have two binding domains bearing reduced affinities of 50 nM to 50 μM, one of which is the inserted or I domain of the α.sub.L subunit of Lymphocyte function-associated antigen-1, and the other one is scFv of EpCAM antibody. The dual CAR T cells of the present invention provide enhanced anti-tumor activity and reduced rate of tumor relapse.

The present disclosure relates to compositions comprising compounds or cells able to specifically bind immunoglobulin kappa (IgKappa) and membrane molecule CD 19 under physiological conditions. In particular, the disclosure relates to a combinatorial chimeric antigen receptor (cCAR) with antigen binding domains specific for the antigen CD19 and the immunoglobulin (Ig) Kappa light chain and their expression in immune effector cells to target cells expressing CD19 and IgKappa, and such immune cells for use in treating B-cell cancers.

Provided herein, inter alia, nucleic acids including coding sequences for human CD80, IL-15, IL-15Rα polypeptides, wherein the coding sequence for hCD80 is operably positioned upstream to the coding sequences for hIL-15 and hIL-15Rα. The disclosure also provides recombinant cells, cell cultures, pharmaceutical compositions, and whole-cell vaccines containing the recombinant cells disclosed herein. Also disclosed are methods useful for treating myeloma and leukemias, such as acute myelogenous leukemia (AML).

The present invention provides a nucleotide sequence for encoding CAR, a ROBO1 CAR-NK cell of expressing the CAR, and preparation and application thereof. The ROBO1 CAR-NK cell provided by the present invention can specifically kill tumor cells by using ROBO1 antibody for the construction of CAR-NK cells and using ROBO1 molecules as target antigens. It can be used as a therapeutic agent for tumor diseases, for the treatment of tumor with highly expressing of ROBO1, without harmful phenomena such as cytokine release syndrome, thus providing new treatments for the tumors which are ineffective in traditional surgery, chemotherapy and radiotherapy. It has lower toxicity, higher safety and better specific lysis activity compared with ROBO1 CAR-T cell.

Modified single chain variable fragments (scFv) that specifically bind CD147 are provided. Also provided are chimeric antigen receptors (CARs) including the modified CD147 scFv, nucleic acids encoding the CARs, vectors including the nucleic acids encoding the CARs, and immune cells expressing the CARs. Methods of treating a subject with cancer including administering to the subject an immune cell expressing a disclosed CD147-CAR are also provided.

The present invention relates to a cell which comprises a chimeric antigen receptor (CAR) comprising a binding domain which binds a first epitope of a tumour antigen; and a polynucleotide which encodes a bi-specific protein which comprises a first binding domain which binds a second epitope of said tumour antigen; and a second binding domain which binds a cell surface antigen. The present invention also provides CAR systems, nucleic acids, vectors, pharmaceutical compositions and pharmaceutical compositions for use in the treatment and/or prevention of disease.

The present invention relates to a cell which comprises a chimeric antigen receptor (CAR) comprising a binding domain which binds a first epitope of a tumour antigen; and a polynucleotide which encodes a bi-specific protein which comprises a first binding domain which binds a second epitope of said tumour antigen; and a second binding domain which binds a cell surface antigen. The present invention also provides CAR systems, nucleic acids, vectors, pharmaceutical compositions and pharmaceutical compositions for use in the treatment and/or prevention of disease.

The present invention relates to tumor antigens and their use in cancer immunotherapy. In particular, the present invention relates to HERV epitopes and tumor associated antigens (TAAs) expressed by liver cancer cells and which, preferably in combination with epigenetic drugs, can be used in tumor vaccination therapies in the treatment and prevention of liver cancer, preferably hepatocellularcarcinoma (HCC).

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The invention provides antigen binding domains that bind myeloid cell surface antigen CD33 protein comprising the antigen binding domains that bind CD33, polynucleotides encoding them, vectors, host cells, methods of making and using them.