The present invention includes compositions and methods for retrieving tumor-related antibodies and antigens. In one aspect, the invention includes a method for Sequential Tumor-related Antibody and antigen Retrieving (STAR) which directly and efficiently identifies potent antibodies that can specifically bind to tumor-related antigens on the tumor cell surface. In another aspect, the invention includes a CAR comprising a nanobody, a transmembrane domain, and an intracellular domain, wherein the nanobody is retrieved by a STAR method. In another aspect, the invention includes a CAR T system that targets CD13 and treats acute myeloid leukemia. In another aspect, the invention includes a CAR T system and ADC that targets CDH17 and treats NETs and other types of tumors expressing this antigen, with tolerable toxicities.

A chimeric antigen receptor targeting to human NKG2DL, its encoding sequence, and its modified immune response cells, and the preparation and application thereof are provided. This invention constructs a chimeric antigen receptor targeting to NKG2DL and its modified immune response cell based on the NKG2D molecule. The amino acid sequence of the chimeric antigen receptor targeting the human NKG2DL is sequentially connected by the following amino acid sequences from an amino terminal to a carboxy terminal: an amino acid sequence of a guiding sequence, an amino acid sequence of human NKG2D, an amino acid sequence of a human CD8 hinge region, an amino acid sequence of a human CD8 transmembrane region, an amino acid sequence of a human 4-1BB intracellular domain and an amino acid sequence of a human CD3 zeta domain.

The invention relates in various aspects to a synthetic chimeric vaccinia virus or compositions comprising such viruses, and the development and use of systems and methods for producing such synthetic chimeric vaccinia viruses. The synthetic chimeric vaccinia viruses are well suited, among others, as virus vaccines or to generate an oncolytic response and pharmaceutical formulations.

Provided is an antibody targeting CLDN18.2. The antibody targeting CLDN18.2 comprises VL and/or VH; the VL comprises the following CDR sequences: a VL CDR amino acid sequence as shown in SEQ ID NO: 11 or SEQ ID NO: 12; a VL CDR2 amino acid sequence as shown in SEQ ID NO: 13; and a VL CDR3 amino acid sequence as shown in SEQ ID NO: 14; and the VH comprises the following CDR sequences; a VH CDR1 amino acid sequence as shown in SEQ ID NO: 15; a VH CDR2 amino acid sequence as shown in SEQ ID NO: 16; and a VH CDR3 amino acid sequence as shown in SEQ ID NO: 17. Further disclosed are a bispecific antibody targeting CLDN18.2, a conjugates of the antibody, a CAR molecule targeting CLDN18.2 and a cell comprising same, and applications thereof.

The present disclosure provides an allogeneic whole cell cancer vaccine platform that includes compositions and methods for treating and preventing cancer. Provided herein are compositions containing a therapeutically effective amount of cells from one or more cancer cell lines, some or all of which are modified to (i) inhibit or reduce expression of one or more immunosuppressive factors by the cells, and/or (ii) express or increase expression of one or more immunostimulatory factors by the cells, and/or (iii) express or increase expression of one or more tumor-associated antigens (TAAs), including TAAs that have been mutated, and which comprise cancer cell lines that natively express a heterogeneity of tumor associated antigens and/or neoantigens. Also provided herein are methods of making the vaccine compositions, methods of preparing, and methods of use thereof.

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.

Provided herein are methods for inducing and maintaining an immune response to a tumor in a subject while treating a primary tumor. The methods include administering to the subject an effective amount of CAR-expressing-NK-92 cells to treat the primary tumor thereby inducing an anti-tumor immune response that is maintained in the subject, the maintained immune response preventing tumor regrowth and/or inhibiting generation of secondary tumors. Also provided are methods of producing an anti-tumor vaccine in a subject with a tumor. The methods include administering to the subject an effective amount of CAR-expressing-NK-92 cells to the subject thereby inducing an anti-tumor vaccine to the tumor in the subject.

The present disclosure provides methods of increasing sensitivity of a tumor to treatment with an immune checkpoint inhibitor (ICI) in a subject and methods of treating a subject with an immune checkpoint inhibitor (ICI)-resistant tumor. The methods comprise administering to the subject a composition comprising a liposome comprising a cationic lipid and mRNA molecules, wherein the liposome is systemically administered to the subject. Also provided are methods of increasing the number of activated plasmacytoid dendritic cells (pDCs) in a subject in need thereof, comprising administering to the subject a composition comprising a liposome comprising a cationic lipid and mRNA molecules, wherein the liposome is systemically administered to the subject. Combination therapy with anti-PD-L1 mAb. Related methods of treatment and methods of preparing a dendritic cell vaccine are additionally provided.

The invention is in the field of medical sciences. It provides means and methods for the treatment of cancer. More in particular, it provides cells and cell lines that can be developed into fully functional dendritic cells. These cells endogenously express cancer-specific antigens, which makes them particularly suited for the treatment of different kinds of cancer. More in particular, the invention relates to a precursor cell line for dendritic cells called DC-One as deposited at the DSMZ under accession number DSMZ ACC3189 on Nov. 15, 2012.

Disclosed are pharmaceutical compositions for inducing an immune response against tumor cells comprising tumor cells which are made apoptotic by treatment with high hydrostatic pressure and dendritic cells, and methods for producing such compositions.