710 results about "Tumor antigen" patented technology

The invention provides compositions and methods for treating cancer by using immune effector cells (e.g., T cells, NK cells) engineered to conditionally express an agent which enhances the immune effector response of an immune effector cell that expresses a Chimeric Antigen Receptor (CAR). The conditional agents described herein include agents that target a cancer associated antigen, e.g., a CAR, agents that inhibit one or more checkpoint inhibitors of the immune response, and a cytokine.

The invention relates to the field of biological medicines, in particular to a tumor antigen peptide and application thereof. The tumor antigen peptide provided by the invention comprises a peptide fragment with an amino acid sequence as shown in SEQ ID No.1. The tumor antigen peptide provided by the invention can be presented by the highest frequency HLA subtype (HLA-A * 11: 01) of Chinese population. In addition, through an in-vitro stimulation mode, it is verified that the tumor antigen peptide can effectively stimulate specific T cells, and a specific TCR element is successfully obtained. Therefore, a direct foundation is laid for further developing a TCR-T therapy, a therapeutic vaccine and other immunotherapies of the targeted human TP53R248Q.

The present application relates to the field of biomedicine, and in particular to a tumor antigen peptide and a use thereof. Provided is a tumor antigen peptide, comprising a peptide segment having an amino acid sequence as shown in SEQ ID NO: 1. The provided tumor antigen peptide can be presented by the HLA subtype (HLA-A*11:01) having a high proportion of Chinese population. Additionally, by means of in vitro stimulation, the tumor antigen peptide is verified to effectively stimulate specific T cells, and a specific TCR element is successfully obtained. The present application lays a direct foundation for further developing TCR-T therapy targeting human TP53 R248Q and immunotherapy such as therapeutic vaccines.

The invention discloses an engineered autologous tumor tissue scaffold and application thereof, and the engineered autologous tumor tissue scaffold is prepared by performing specific treatment on autologous tumor tissue to induce immunogenic cell death of the tumor tissue, and then sequentially performing freezing and drying steps; the engineered autologous tumor tissue scaffold can be used for loading dendritic cells and constructing personalized tumor vaccines. According to the stent, autologous tumor tissue is adopted, so that a specific and comprehensive tumor antigen pedigree is reserved, and multi-epitope immunostimulation is provided; and meanwhile, excellent biocompatibility is ensured, the immunological rejection risk is reduced, and relatively high safety is ensured.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.

The invention discloses an HLA-A * 11: 01 renal cell carcinoma tumor antigen short peptide derived from an IDO1 gene. The invention provides a tumor antigen peptide. The amino acid sequence of the tumor antigen peptide is as shown in SEQ ID No. 1. Researches find that a compound formed by the oligopeptide and a corresponding HLA molecule (HLA-A * 11: 01) can be recognized by T cells, and immune response is activated. The invention provides a potential target spot for treatment of renal cell carcinoma, and provides a new target spot screening direction for subsequent tumor antigen treatment of renal carcinoma.

The invention relates to the technical field of biological medicine, in particular to the field of cell therapy, and particularly relates to application of STAR and immune cells comprising the STAR to treatment and / or prevention of tumors, an antigen binding region of the STAR comprises one or more than two of an antibody, a ligand or an antibody fusion body which binds to LILRB4, the antibody such as scFv or VHH, and the ligand and the antibody fusion body can be combined with the LILRB4. Wherein the LILRB4 is used as a tumor antigen and / or a receptor in an immunosuppressive active cell. According to the invention, the targeted killing effect of immune cells on tumors is enhanced by targeting tumor cells and / or reducing immune escape caused by immunosuppressive active cells.

Drug delivery nanoparticle compositions and methods for the treatment of a cancer are provided that can be used individually or in combination. These compositions and methods include: (1) exogenous vaccination using neoantigens or tumor-associated antigens to potentiate an anti-tumor immune response; (2) nanoparticle-based drug delivery targeting the liver, aimed at reprogramming the hepatic immune environment to reduce or eliminate tumor antigen tolerance, thereby enhancing the immune system's ability to combat metastatic cancer; and (3) expansion of the liver metastasis treatment platform to target tumor-associated lymphoid structures, supporting the immune response at the primary tumor site. Any of these methods may be optionally combined with chemo-immunotherapy for enhanced efficacy.

A fusion protein comprising: a first component comprising an antibody, or a fragment or variant thereof; and a second component comprising a cytokine trap or an adenosine deaminase or a fragment or variant thereof. In certain embodiments, the antibody is an anti-PD-1 antibody. In certain embodiments, the antibody binds to a tumor antigen, for example a MUC16 or MUC1 antigen. In certain embodiments, the cytokine trap is a TGF-β trap. A polynucleotide encoding such a fusion protein and a vector comprising such a polynucleotide. A composition comprising the fusion protein. A method of using the composition, including in the treatment of cancer.

There is provided an antibody or fragment thereof wherein the antibody comprises: (a) a heavy chain variable region (VH) wherein the VH comprises a complementarity determining region (CDR) selected from the group consisting of (i) H-CDR1, H-CDR2 and H-CDR3 as shown in any one of SEQ ID NO.1 to 24 or 49 to 88, respectively, and / or (b) a light chain variable region (VL) wherein the VH comprises a complementary determining region (CDR) selected from the group consisting of: (i) H-CDR1, H-CDR2 and H-CDR3 as shown in any one of SEQ ID NO.1 to 24 or 49 to 88; wherein the VL comprises a complementarity determining region (CDR) selected from the group consisting of: (i) L-CDR1, L-CDR2, and L-CDR3 as shown in any one of SEQ ID NO.25 to 48 or 89 to 128, respectively. Preferably, both VH and VL chains are used. Antibodies and fragments thereof have utility in the treatment of cancer.

The invention relates to the field of biological medicines, in particular to a chimeric cytokine activated receptor for activating lymphocytes by using soluble immunosuppressive molecules and application of the chimeric cytokine activated receptor in tumor treatment. The chimeric cytokine activation receptor and a chimeric antigen receptor for recognizing tumor antigens are connected in parallel to form a co-expressed polycistron structure. Wherein the chimeric cytokine activation receptor comprises an scFv structural domain, a transmembrane structural domain and a cytokine chimeric activation structural domain which specifically recognize and bind soluble immunosuppressive molecules. The CAR-NK cell can specifically recognize soluble inhibitory factors in the tumor microenvironment and improve the in-vivo and in-vitro anti-tumor efficacy of the CAR-NK cell, and can be used for treating solid malignant tumors.

The invention discloses a tumor whole cell wrapped by a metal-polyphenol nano coating as well as a preparation method and application thereof. The preparation method comprises the following steps: step 1, fully mixing a plant polyphenol solution and a tumor cell suspension; 2, adding a manganese ion-containing compound solution, and fully mixing; 3, adding a buffer solution into the solution obtained in the step 2, fully mixing, washing, and centrifugally separating to obtain tumor cells coated with coatings; the plant polyphenol and the manganese ions can be quickly assembled at room temperature, a compact nano coating is formed on a tumor cell membrane, and tumor cells are inactivated due to the wrapping of the nano coating, so that the safety of the vaccine is ensured; the nano coating can prevent any potential tumor antigen from being lost under physiological conditions; lipopolysaccharide is further modified, so that the formed LMP whole-cell vaccine can be promoted to be endocytosed by antigen presenting cells; the metal manganese ions can stimulate the STING pathway to enhance the anti-tumor effect while forming the structural coating.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.

The present invention discloses an improved polypeptide tumor vaccine composition and application, specifically relating to the field of polypeptide tumor vaccines, the vaccine comprises a nucleic acid sequence encoding a plurality of mutant tumor-associated antigens, the nucleic acid sequence including but not limited to: a nucleic acid sequence encoding a mutant WT1 antigen, selected from the amino acid sequence of SEQ ID NO: 1 or a variant thereof with at least 90% identity; a nucleic acid sequence encoding a mutant MUC1 antigen, selected from the amino acid sequence of SEQ ID NO: 2 or a variant thereof with at least 90% identity; a nucleic acid sequence encoding a mutant PD-1 antigen, selected from the amino acid sequence of SEQ ID NO: 3 or a variant thereof with at least 90% identity; and the vaccine composition further comprises one or more modified elements that enhance antigen expression or immune response, including a signal peptide, an adjuvant coding sequence or an immunostimulatory sequence. The vaccine composition of the present invention is intended to enhance the immune response to a plurality of tumor antigens and improve the effectiveness of tumor treatment.

The invention discloses an HLA (Human Leukocyte Antigen)-A * 11: 01 renal cell carcinoma tumor antigen short peptide derived from long-chain non-coding RNA (Ribonucleic Acid) LINC02717. The invention provides a tumor antigen peptide. The amino acid sequence of the tumor antigen peptide is as shown in SEQ ID No. 1. Researches find that a compound formed by the oligopeptide and a corresponding HLA molecule (HLA-A * 11: 01) can be recognized by T cells, and immune response is activated. The invention provides a potential target spot for treatment of renal cell carcinoma, and provides a new target spot screening direction for subsequent tumor antigen treatment of renal carcinoma.

The invention relates to the technical field of biology, in particular to a tumor postoperative vaccine as well as a preparation method and application thereof. The method comprises the following steps: resuspending tumor cells in a first solution containing metal ions for incubation, collecting the tumor cells, resuspending the tumor cells in a second solution containing mineralized ions for incubation, enabling the metal ions to react with the mineralized ions to obtain metal inorganic salt, forming a mineralized shell layer on the surfaces of the tumor cells, and resuspending the tumor cells to obtain the tumor postoperative vaccine. And due to the mineralized shell layer, the vaccine has the capability of activating a signal channel in an antigen presenting cell through mechanical stimulation, so that an immune system is favorably activated, and the anti-tumor capability of the vaccine is improved. In addition, tumor cells are inactivated in the vaccine preparation process and keep a complete form, and presentation of a complete tumor antigen is facilitated, so that a relatively good anti-tumor effect is obtained.

The invention belongs to the technical field of tumor vaccines, and particularly relates to an mRNA (messenger Ribonucleic Acid) vaccine for coding tumor antigen epitopes as well as a preparation method and application thereof. In order to overcome the defect of immune escape caused by insufficiency or loss of a single antigen, the invention provides an mRNA vaccine capable of simultaneously coding a plurality of tumor antigen epitopes, and the tumor antigen epitopes are selected from high-frequency mutation epitopes of human tumor driving genes, such as G12D, G12V and G12C mutations of RAS genes; the antigenic epitopes can be used for preparing antigenic epitopes related to common viruses of human tumors, such as HPV16E6 / E7, EBV LAMP1 or CMV pp65, and tumor high-expression carcino-embryonic antigen gene epitopes, such as MAGE-A4, NY-ESO-1, WT1, and the like. The mRNA vaccine is obtained by serially expressing a plurality of tumor antigen epitopes and encapsulating and delivering lipid nanoparticles. Experiments prove that the compound can effectively prevent and treat various tumors and has a wide application prospect.

The invention belongs to the field of nano biomedicine, and particularly discloses a yeast bionic vaccine based on a metal organic framework ZIF-8 as well as a construction method and application of the yeast bionic vaccine, and the structure of the bionic vaccine is that ZIF-8 loaded with antigen OVA is encapsulated in a yeast shell. The invention relates to preparation and anti-tumor immune response of the bionic vaccine. The yeast shell is obtained by performing acid and alkali treatment and organic solvent washing on saccharomycetes and has the effects of targeting antigen presenting cells and stimulating immune response, and the antigen-loaded metal organic framework ZIF-8 is encapsulated in the yeast shell and has relatively good stability and an effect of continuously releasing antigens. The ZIF-8 is decomposed in antigen presenting cells, and lysosome escape of the antigen is induced. The yeast bionic vaccine provided by the invention can specifically target antigen presenting cells, continuously release tumor antigens in vivo, mediate escape of lysosome of the antigens and stimulate strong anti-tumor immune response, and has a better application prospect.

Provided herein are methods and compositions for treating chordoma by preferentially targeting cancer stem cells than non-cancer stem cells in chordoma to effectively treat chordoma. In some embodiments, the chordoma tumors cells (preferentially the cancer stem cells in chordoma) are targeted by modified NK-92 cells (i.e., haNK® cells) that express CARs that comprise means for binding to the PD-L1 and another tumor-specific antigen (e.g., EGFR). In some embodiments, the chordoma tumor cells are targeted by using NK cells in combination with a means for binding to means for binding to the PD-L1 and / or a means for binding another tumor antigen (e.g., EGFR). Each of the treatment methods disclosed above may be implemented prior to, and / or concurrent with radio- and / or chemotherapy, and / or may be employed with immune therapy as is discussed in more detail below.

The present invention discloses a method for expansion of natural killer (NK) cells or CAR-NK cells using peripheral blood mononuclear cells (PBMCs) and culturing the cells in a medium comprising a feeder layer having a population of mesenchymal stem cells (MSCs) with disrupted or deleted MHC class I gene and / or MHC class II gene and a heterologous gene for expressing Interleukin-21 (IL-21), and Interleukin-2 (IL-2). The present disclosure further provides a method and a model for evaluating natural killer (NK) cells or CAR-NK cells using tester line comprising induced Pluripotent stem cells (iPSCs) comprising disrupted or deleted MHC class I gene and / or MHC class II gene and a heterologous gene encoding a tumor antigen.

The invention relates to preparation of a pancreatic cancer dendritic cell vaccine and application of the pancreatic cancer dendritic cell vaccine in treatment of pancreatic cancer, relates to the technical field of biological medicines, and comprises a preparation method of Panc-1 and AsPC-1 lysates, a preparation method of a DC vaccine loaded with the Panc-1 and AsPC-1 lysates and function verification of DC cells. The DC vaccine prepared by the invention not only stimulates T cells to generate more IFN-gamma, but also induces to generate stronger tumor killing T cells, and provides a new thought for research and development of pancreatic cancer DC vaccines. In addition, Panc-1 and AsPC-1 lysates are adopted as antigens of the DC vaccine, so that the problem that autologous tumor antigens are difficult to obtain is solved. Furthermore, Panc-1 and AsPC-1 lysates are adopted as antigens of the DC vaccine, and the mixed lysates contain abundant and wide tumor antigens and can prevent immune escape of tumors.

Provided herein is a conjugate comprising a branching group which is at least trivalent, an antibody or antibody mimetic specifically binding to a tumor antigen expressed on a tumor cell, an effector moiety, and a potency enhancing group.

A trispecific antigen binding protein, relating to a trispecific antibody that specifically binds to two tumor antigens of GPRC5D and BCMA and a T cell surface antigen CD3, and a pharmaceutical composition containing the trispecific antibody, a preparation method for the trispecific antibody and a use of the trispecific antibody.

A curcumin-containing nano-drug for treating cancer, a preparation method therefor, and use thereof. The nano-drug comprises curcumin and an extracellular vesicle expressing an anti-cancer protein TRAIL, or the nano-drug comprises curcumin and a tumor-antigen binding polypeptide-modified extracellular vesicle expressing an anti-cancer protein TRAIL. The curcumin is loaded into the extracellular vesicle for combined use, such that an extremely strong synergistic effect can be generated; the anti-cancer activity of the EV-T can be significantly enhanced by means of polypeptide modification; the composite nano-drug obtained by loading the curcumin into the extracellular vesicle can solve the problem of insolubility of curcumin, thereby further improving the anti-cancer effect.

The invention provides a preparation method of DC cells. The preparation method is especially suitable for rapidly obtaining high-purity and high-functional-activity DC cells. The method comprises the steps of separation from peripheral blood mononuclear cells (PBMC), induction culture, maturation treatment and the like, maturation of the dendritic cells is promoted by introducing an anti-CD47 single-domain antibody or LPS, and the immunocompetence of the dendritic cells is remarkably improved. The method is further applied to preparation of an anti-tumor cell preparation, the capability of activating tumor specific T cells by tumor antigen-loaded DC cells can be remarkably enhanced, and the killing activity of the T cells to tumor cells is improved. The preparation method provided by the invention overcomes the defects in the prior art, has the advantages of high efficiency, safety and stability, and can provide a more reliable cell therapy scheme for tumor immunotherapy.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are gene edited (e.g., using Crispr / Cas) to modulate, reduce, or otherwise eliminate expression of one or more endogenous genes. In several embodiments, the edited cells are engineered to express chimeric antigen receptors that target tumor antigens (e.g., CD19, ligands of the NKG2D receptor, CD70, and / or BCMA, etc.). In several embodiments, the editing enhances one or more aspects of immune cell efficacy in cellular immunotherapy, including cytotoxicity (e.g., ADCC) and / or persistence.

The present invention relates to antigen-based immunotherapy, in particular cancer immunotherapy. In particular, the present invention provides an antigen peptide which is different from a fragment of a human tumor antigen but has amino acid similarity to the fragment of the human tumor antigen. The invention also provides immunogenic compounds, nanoparticles, cells and pharmaceutical compositions comprising such antigen peptides and nucleic acids encoding such antigen peptides.

The invention provides an anti-CD28 humanized single-domain antibody and a preparation method of the anti-CD28 humanized single-domain antibody. Specifically, the invention discloses a plurality of single-domain antibodies targeting CD28, humanized antibodies thereof, derived proteins, gene sequences for encoding the single-domain antibodies and the humanized antibodies, and expression vectors and expression systems for producing the single-domain antibodies and the humanized antibodies. The single-domain antibody provided by the invention is a CD28 non-agonistic antibody, can block the binding of CD28 and CD80, and can specifically bind to CD28 of human and monkeys. The single-domain antibody provided by the invention has high safety, and provides a research and development basis for development of antibody coupling drugs and multispecific antibody drugs. A bispecific antibody composed of the CD28 single-domain antibody and the targeting tumor antigen antibody can significantly enhance the activity of the CD3 bispecific antibody. The activity of a multi-specific antibody composed of the CD28 single-domain antibody, the targeting tumor antigen antibody and the CD3 antibody is significantly superior to that of the CD3 bispecific antibody.

The invention relates to the technical field of biological medicine, and provides a ginseng cell engineering tumor vaccine as well as a preparation method and application thereof. The ginseng cell engineering tumor vaccine comprises an exosome derived from a recombinant ginseng cell capable of expressing a tumor antigen; the recombinant ginseng cell capable of expressing the tumor antigen is obtained by introducing a recombinant plasmid containing tumor antigen DNA into a ginseng cell. According to the invention, ginseng cells in Chinese herbal medicines are taken as host cells for recombinant expression of tumor antigens, large-scale production of tumor vaccines can be realized through construction of an engineering recombinant cell system, biocompatibility and uniformity of the vaccines can be maintained, and safety risks can be reduced. Meanwhile, the prepared tumor antigen recombinant expression ginseng cell exosome can integrate the antigen, an adjuvant and a carrier, and the antigen phagocytosis, maturation and antigen peptide presentation capabilities of APCs are enhanced.

The invention provides a preparation method of a fragmented tumor antigen. The preparation method comprises the following steps: obtaining a tumor cell suspension; and irradiating and incubating the tumor cell suspension to prepare the fragmented tumor antigen. The preparation method is simple, low in cost and convenient to store, the fragmented tumor antigen prepared through the preparation method can remarkably inhibit tumor growth in vivo after being inoculated to an individual, tumor metastasis and relapse can also be effectively inhibited, immune memory is induced to be generated, the continuous anti-tumor effect is achieved, and the preparation method is suitable for clinical application. The control on metastatic tumors is obviously improved. The effective anti-tumor effect can be achieved in vivo when the fragmented tumor antigen prepared by the invention is independently or jointly used.