The invention relates to a chimeric gallinaceous bird embryo comprising both types of exogenous cells: a. At least one population of cancer cells, and b. At least one population of immune cells, wherein said exogenous cancer cells are present in at least one tissue of said embryo, and said exogenous immune cells are present in at least one tissue of said embryo and/or circulate in the blood vessels of said embryo.

Provided herein, inter alia, are compositions and methods including recombinant oncolytic viruses expressing human IL-15 and human IL-15Rα-sushi domain for the treatment of cancer and immune disorders. The recombinant oncolytic viruses may be used in combination with immune cells expressing chimeric antigen receptors (CAR) targeting EGFR and EGFR mutants.

Provided are CAR-T compositions that are directed to GPC3, including chimeric receptors, and engineered immune cells to GPC3. The disclosure also provides vectors, compositions, and methods of treatment using GPC3 antigen binding molecules and engineered immune cells. GPC3 CAR compositions provided herein can be used for the treatment of certain cancers.

An antigen-loaded nanogel is formed by loading or encapsulating one or more long peptide antigens or one or more protein antigens in a hydrophobized polysaccharide. The long peptide antigen(s) or protein antigen(s) contains (or each contain) one or more CD8+ cytotoxic T cell recognition epitopes and/or one or more CD4+ helper T cell recognition epitopes, which is/are derived from the antigen. The antigen-loaded nanogel is administered at least one day prior to administration of antigen-specific T cells to improve the efficacy of a T cell infusion therapy against an immune checkpoint inhibitor-resistant tumor. The hydrophobized polysaccharide may be pullulan having cholesteryl groups bound thereto. An immune-enhancing agent also may be administered in or with the antigen-loaded nanogel.

The present invention provides synthetic polypeptides comprising an annexin V protein, or a functional portion or fragment or variant thereof, conjugated to a tumor antigen, or a functional portion or fragment or variant thereof. The invention further provides methods for making said synthetic polypeptides and their use in the treatment of proliferative diseases such as cancer and tumors originating therefrom.

The present invention relates to a pharmaceutical composition comprising a compound of formula (I) ##STR00001##
and methods of treating or preventing cell proliferation disorders comprising administering to a subject a therapeutically active amount or a preventive amount of such a compound.

Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals, in some embodiments, comprise a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).

The present invention encompasses the recognition that identification of alternative means to block RAS oncogenic signaling may be required for developing novel cancer therapies. Among other things, the present invention encompasses the recognition that targeting RAS palmitoylation can achieve effective therapy for RAS-related cancers. Furthermore, the present invention encompasses the recognition that reduction of ZDHHC9 level and/or activity can significantly reduce palmitoylation level of Ras protein. Among other things, the present invention encompasses the recognition that identification of agents that modulate expression and/or activity of ZDHHC9 can reduce palmitoylation level of Ras protein. In some embodiments, the present invention provides methods of treating a subject suffering from cancer by administering ZDHHC9 inhibition therapy.

The invention provides in vivo methods for identifying cancer-associated immunotherapy targets.

Disclosed herein are antigenic peptide-MHC complexes, termed comPACT polypeptides and comPACT polynucleotides, and methods of producing such complexes. Also discloses herein are methods of producing libraries of comPACT polynucleotides and polypeptides, and their exemplary use in capturing cancer neoepitope-reactive T cells with high accuracy. Dual particle detection approaches for detection of neoantigen specific T cells with improved sensitivity and specificity are provided. Signal to noise ratio analysis of isolated T cells for detection of neoantigen-specific T cells with improved T cells is also provided.