The invention relates to nucleic acid agents modulating the expression of SLAMF6 isoforms, compositions comprising same and methods for their use in immunomodulation. Specifically, provided are splice-switching oligonucleotides and constructs useful in cancer immunotherapy.

The present invention provides a method for treating a disease in a subject, which comprises the step of administering to the subject a plurality of cells which express: (a) a chimeric antigen receptor (CAR); and (b) a mutant version of calcineurin A and/or calcineurin B which is resistant to the calcineurin inhibitor. The subject may be receiving or have received treatment with a calcineurin inhibitor. The CAR-expressing cells may be administered prior to, following, simultaneously with or in combination with a calcineurin inhibitor.

The invention relates to cancer management, specifically to therapeutic combinations and methods for immunotherapy of tumors and malignancies. More specifically, embodiments of the invention provide compositions, methods, pharmaceutical packages and combined preparations employing the use of a SLAMF6-mediated T cell activator in combination with a LAG3 inhibitor.

The invention provides compositions, methods, and vaccines that may stimulate the immune system and that may be used for treating malignancies associated with overexpression of the HER3 protein. Such compositions include epitopes of the HER3 protein.

An antigen-binding protein targeting CD70. In particular, the present invention relates to a chimeric antigen receptor containing the antigen binding protein and the use thereof, and cells containing or expressing the antigen binding protein. The antigen-binding protein binds to a CD70 protein at 1 nM of a K.sub.D value. The chimeric antigen receptor containing the antigen-binding protein has strong specific recognition and binding abilities to the CD70 protein. The cells containing or expressing the antigen-binding protein can secrete cytokines IL-2 and IFN-.

Described herein are antigen binding proteins with specificity to Melanoma-Associated Antigen A4 (MAGE-A4) peptide-MHC (pMHC). Also described are multispecific antigen binding proteins comprising an antigen binding domain with specificity to CD3, and at least one MAGE-A4 pMHC antigen binding domain. Methods of treating cancer with the same are also described.

The present invention provides a chimeric antigen receptor (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Disclosed herein are carcinoembryonic antigen 6 (CEA6)-specific binding polypeptides. These binding polypeptides may be incorporated into chimeric antigen receptors (CARs). Also disclosed herein are methods of using these binding polypeptides and/or CARs for the treatment of, for example, a cancer.

Disclosed herein are mesothelin (MSLN)-specific binding polypeptides. These binding polypeptides may be incorporated into chimeric antigen receptors (CARs). Also disclosed herein are methods of using these binding polypeptides and/or CARs for the treatment of, for example, a cancer.

Circular RNA, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes an antigen. In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.