502 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 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.

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.

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 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.

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 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.

The invention relates to the technical field of biological medicines, in particular to a CKAP4-targeted tumor antigen peptide, a vaccine and application of the CKAP4-targeted tumor antigen peptide. The invention provides a high-immunogenicity tumor antigen peptide RLTELTKSI targeting human and mouse homologous CKAP4 protein, and the tumor antigen peptide and a vaccine thereof can realize efficient killing of CKAP4 positive tumor cells and remarkable inhibition of CT26 subcutaneous tumor by activating specific CD8 + T cell immune response. The traditional single-target limitation is broken through, the co-expression characteristic of CKAP4 in tumor cells and immunosuppressive cells (TAM / TAN) is utilized, a double-target and double-channel mechanism is initiated, and the immunosuppressive state of cold tumors is effectively reversed by inducing T cells to synchronously kill tumor cells and remodel an immune microenvironment. According to the technology, CKAP4 is expanded from an antibody target to a T cell vaccine target, lasting specific CTL response can be stimulated, the off-target risk of antibody treatment is avoided, a universal treatment scheme can be provided for solid tumors, and the clinical transformation potential and the treatment broad spectrum are remarkably improved.

This invention provides antibodies or functional antibody fragments or probes thereof targeting a unique set of antigens recognized in cancer. The invention comprises a nucleotide sequence derived from the L2A5 monoclonal antibody. The antibodies or functional antibody fragments or probes thereof include variable heavy chain domains and variable light chain domains having the amino acid sequences provided herein. The DNA / amino acid sequence binding is unique and has never been previously described. The invention further provides antibodies or functional antibody fragments or conjugates or recombinant proteins useful for the detection, treatment, and prevention of human diseases, including cancer.

This disclosure is directed to payload bioactive agents (PBAs) that include modified exatecans. This disclosure is also directed to bioactive compositions and pharmaceutical compositions for treating cancer. The pharmaceutical compositions comprise a polymer, a targeting bioactive agent (TBA), a PBA comprising a modified exatecan that is covalently linked to the TBA directly or indirectly, a linker that can comprise a cleavable linker, and a pharmaceutical suitable carrier. The pharmaceutical compositions can be antibody-drug conjugates (ADCs) for treating cancers, with the potential for treating tumors having negative or low (AgLow) tumor antigens.

The present invention relates generally to the use of LSD1 inhibitors in connection with use and manufacture of immune effector cells (e.g., T cells, NK cells), e.g., engineered to express a chimeric antigen receptor (CAR), to treat a subject having a disease, e.g., a disease associated with expression of a tumor antigen.

The invention discloses an anti-tumor pharmaceutical composition based on NBDHEX and application of the anti-tumor pharmaceutical composition in treatment of immunosuppressive malignant tumors. The pharmaceutical composition comprises NBDHEX (6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol) and a PD-1 (programmed death-1) inhibitor, and is characterized in that the NBDHEX (6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol) and the PD-1 inhibitor are used as raw materials. The NBDHEX can induce tumor cells to generate immunogenic death and promote tumor antigen release, DAMPs signal activation and dendritic cell maturation, so that an immunosuppressive tumor microenvironment is remodeled, and CD8 + T cell infiltration and effector functions are enhanced. The pharmaceutical composition can significantly improve the anti-tumor immune response intensity and the treatment response rate. Animal experiments and cell experiments verify the synergistic anti-tumor effect of the composition in a lymphoma model. The immunosuppressive malignant tumors are suitable for treatment of various immunosuppressive malignant tumors including lymphoma, and are especially suitable for patients with poor single-drug reaction or drug resistance to immune checkpoint inhibitors, and a new way is provided for clinical treatment of tumors.

The invention belongs to the technical field of cellular immunity, and relates to a non-virus-dependent engineering induced pluripotent stem cell as well as a preparation method and application thereof. A coding gene of a chimeric antigen receptor is inserted into an SIRPA gene on a genome of the engineered induced pluripotent stem cell. According to the invention, iPSC cells are edited in a SIRPA gene position fixed-point insertion mode, simultaneous knockout of SIRPA and integration of an exogenous chimeric antigen receptor CAR are realized, and CAR-iMac can be further induced and differentiated, so that CAR-iMac is differentiated to mononuclear / macrophage tumor targeted cells, the phagocytic ability of CAR-iMac is enhanced, tumor antigens are further presented, the tumor immune microenvironment is improved, and the anti-tumor immunity is enhanced; the method effectively solves the corresponding problem of directly extracting the natural macrophages from the human body, reduces the production cost and the time cost, is beneficial to clinical application, and in addition, utilizes a non-virus-mediated gene editing means to remarkably improve the genetic silencing phenomenon.

The invention relates to the technical field of biological medicine, and provides a Chinese herbal medicine vesicle-LNP hybrid tumor mRNA vaccine and application thereof. The tumor mRNA vaccine disclosed by the invention is obtained by hybridizing Chinese herbal medicine nano-vesicles and lipid nano-particles loaded with tumor antigen mRNA. According to the invention, the characteristic of good biocompatibility of Chinese herbal medicines is utilized, so that the safety risk of the cationic lipid carrier is reduced. By combining the characteristics of Chinese herbal medicines, the nano-vesicles are extracted, so that the LNP is promoted to more effectively target antigen-presenting cells, the uptake level of the antigen-presenting cells is promoted, the phagocytosis of mRNA is enhanced, and the targeting and transcriptional expression level of mRNA can be enhanced. Finally, the Chinese herbal medicine nano vesicle-LNP hybrid tumor mRNA vaccine can strengthen the curative effects of inhibiting tumor progression, tumor recurrence and tumor metastasis after the tumor mRNA vaccine is inoculated, and a path is opened up for the combination of the tumor mRNA vaccine and richer immunotherapy means.

A method for treating tumors using a combination of an oncolytic virus vaccine and immune cells. The method specifically includes the following step: treating the tumors by using a combination of the immune cells and the oncolytic virus vaccine; the oncolytic virus vaccine includes a recombinant oncolytic virus expressing a tumor antigen and is used for targeting the tumor cells; the immune cells express a chimeric antigen receptor paired with the tumor antigen, and are used for killing or destroying the tumor cells targeted; the recombinant oncolytic virus includes an M protein, G protein, N protein, P protein and L protein subjected to site-directed mutagenesis. The tumor antigen expressed by the oncolytic virus vaccine can guide the immune cells to reach the target tumor tissue center, achieving a curative effect where 1+1 is greater than 2, with a tumor cell killing rate being up to 100% at most.

The present invention provides a CAR mRNA embedded with lipid nanoparticles to transfect immune NK cells and produce functional CAR-NK cells. The CAR-NK cells target tumor antigens to kill tumors. The present invention provides several advantages: transient expression of CAR-NK cells, lower toxicity, and lower production costs.

Disclosed are a metal-polyphenol nano-coating-wrapped tumor whole cell, a preparation method therefor, and use thereof. A plant polyphenol in the present invention and manganese ions can be rapidly assembled at room temperature to form a dense coating on the membrane of a tumor cell. The nano-coating wrapping inactivates the tumor cell, ensuring that the vaccine is safe. The nano-coating can prevent any potential tumor antigen from being lost under physiological conditions. The nano-coating is further modified with a lipopolysaccharide, which can promote the endocytosis of the formed whole-cell vaccine by antigen-presenting cells. While forming the structural coating, ions of the metal manganese can stimulate the STING pathway to enhance the anti-tumor effect.

Provided herein are tumor-antigen VGLL1 specific T cell receptors. The TCR may be utilized in various therapies, such as autologous cell transplantation, to treat a cancer. Methods for expanding a population of T cells that target VGLL1 are also provided.

Provided are an activity-regulatable IL-12 fusion protein and the use thereof. The fusion protein comprises a first structural unit, a second structural unit, and a third structural unit. The first structural unit is selected from a first Fc fragment, or a first antibody or an antigen-binding fragment thereof, wherein the first antibody or the antigen-binding fragment thereof has the binding activity to a tumor antigen or an immune checkpoint; the second structural unit is selected from a cleavable linker or a non-cleavable linker; and the third structural unit comprises an IL-12 cytokine or a functional fragment thereof. The second structural unit mediates the steric hindrance of the first structural unit to mask the activity of the IL-12 cytokine in the third structural unit, thereby reducing the toxic side effects of in-vivo use of the IL-12 cytokine. Compared with a wild-type IL-12, the fusion protein has the advantage of high safety, and can be further fused with an antibody Fab, scFv or VHH, an antigen-binding peptide or a recombinant protein, a polypeptide, etc. to obtain a multifunctional fusion protein that can be conditionally released and activated.

The invention discloses a nano vaccine as well as a preparation method and application thereof. The nano vaccine provided by the invention is prepared by fusing a liposome of which the surface is coupled with an inhibitor of an inhibitory immune checkpoint and a cell membrane of a tumor antigen sensitized dendritic cell cultured by utilizing a tumor cell lysate and keyhole limpet hemocyanin. The obtained nano vaccine is uniform in particle size, the outer layer of the nano vaccine is wrapped by a cell membrane, and the nano vaccine has proper surface potential, size and structural flexibility and is beneficial to aggregation in tumors. After the nano vaccine reaches tumor tissues, antigens can be efficiently and directly presented to T lymphocytes through cell membranes of tumor antigen sensitized dendritic cells, a costimulatory signal necessary for T cell activation is fully provided, meanwhile, T cell depletion can be reversed through an immune checkpoint inhibitor, the function of the inhibited T cells is re-excited, and the T cells are activated. The cytotoxic function and the multiplication capacity of the T cells are effectively and specifically recovered through a double-line strategy.

Provided are the construction, preparation and use of a functionally enhanced universal CAR-DNT cell. Specifically, provided is a chimeric antigen receptor construct. A CAR function-enhancing element and IL-10 are sequentially fused to the C-terminus of a tumor antigen-targeting CAR via a self-cleaving peptide, and the CAR construct is introduced into a DNT cell, thereby obtaining a functionally enhanced universal CAR-DNT cell, namely, an IL10-CD19-CAR-mbIL15-DNT cell. The cell specifically targets CD19, and has a stronger and more sustained cell killing activity and better safety, thus providing a new therapy for CD19-mediated diseases.