418 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 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.

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 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 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.

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.

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.

The present invention relates to a patient-specific tumor treatment targeting individual expression patterns of tumor antigens, in particular shared tumor antigens, and individual tumor mutations. In one aspect, the present invention relates to a method for preventing or treating cancer in a patient comprising the steps of. (i) inducing a first immune response against one or more tumor antigens in the patient, and (ii) inducing a second immune response against one or more tumor antigens in the patient wherein the second immune response is specific for cancer specific somatic mutations present in cancer cells of the patient.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's.

This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize epitope(s) from tumor antigen NDC80 CT. Accordingly, aspects of the disclosure relate to an engineered T-cell Receptors (TCRs), nucleic acids encoding the TCRs, and cells comprising the nucleic acids and TCRs. Also provided are compositions comprising the cells, nucleic acids, or engineered TCRs of the disclosure, methods of making the cells and methods of using the embodiments of the disclosure for therapeutic treatments.

Disclosed herein are high performance biomarkers and kits for the early detection of small cell lung cancer (SCLC), which can be used to identify, diagnose and treat SCLC patients in the early stage. Methods of diagnosing and treating SCLC in a subject can include detecting the presence of an autoantibody that specifically binds to one or more epitopes of an antigen in a biological sample obtained from the subject, wherein the one or more epitopes of the antigen comprise a post-translational modification; diagnosing the subject with SCLC when the presence of the autoantibody is detected in the biological sample; and treating the SCLC in the subject by administering a chemotherapy regimen, an immunotherapy regimen, an antibody, surgical and / or radiation therapy. In one example, post-translational modifications targeted by autoantibodies include citrullination, isoaspartic acidification, and / or cancer-specific glycosylation.

The present disclosure provides compositions and methods for the detection and treatment of cancer. Specifically, the compositions of the present technology include novel DOTA-haptens that may be complexed with a radioisotope (e.g., 225Ac). Also disclosed herein are methods of the using the DOTA-haptens of the present technology in diagnostic imaging as well as pretargeted radioimmunotherapy.

A conjugate comprises (a) a single domain antibody (sdAb) that specifically binds to a tumor antigen, (b) a drug, and (c) a functional linker that links the drug to the sdAb. The conjugate is used for treating cancer. A method for preparing the conjugate comprises conjugating the functional linker and the drug to the sdAb.

Lung cancer remains the leading cause of cancer-related deaths in the world. Despite the fact that introduction of immune checkpoint inhibitors (ICIs) led to a major advancement in lung cancer treatment, disease prognosis continues to remain low and a significant proportion of patients do not respond to such therapies. Cancer vaccines could potentially provide a complementary approach to boost antitumor immunity and act synergistically with ICIs. Novel tumor antigens shared by a large proportion of lung tumor cells are described herein. Several of the tumor antigens described herein derive from aberrantly expressed unmutated genomic sequences, such as intronic and intergenic sequences, which are not expressed in normal tissues. Nucleic acids, compositions, cells and vaccines derived from these tumor antigens are described. The use of the tumor antigens, nucleic acids, compositions, cells and vaccines for the treatment of lung cancer is also described.

The present application provides a CD4 helper T cell epitope fusion peptide, its encoding nucleic acid and an immune composition comprising the same. The epitope fusion peptide comprises a cytomegalovirus epitope. The epitope fusion peptide provided by the present application can greatly improve the cellular immune response level of the target immunogen, especially a weak immunogen, and is an effective means to overcome the immune system's immune tolerance to antigens, especially tumor antigens or infection-related antigens, and is suitable for efficiently enhancing the efficacy of vaccines.

The application belongs to the technical field of biological nanomaterials, and particularly relates to an immune activation nanosheet as well as a preparation method and application thereof. The immune activation nanosheet comprises a two-dimensional montmorillonite nanosheet with a sheet layer structure, and manganese ions and tumor antigens loaded in the interlayer of the two-dimensional montmorillonite nanosheet. The mass ratio of the manganese ions to the montmorillonite is 1:5-1:20, and the mass ratio of the tumor antigens to the montmorillonite is 1:1-1:10. The immune activation nanosheet has the characteristics of good oral stability, high mucosal targeting, strong immune efficacy, etc. The stability of the immune activation nanosheet in the gastrointestinal tract is good, the immune activation nanosheet can be effectively enriched in the small intestine, a vaccine inoculation pool is formed, the intestinal immune tolerance can be overcome, the immune effect is enhanced, and the immune activation nanosheet has a clinical application prospect.

The name of the invention is T cell activation antibodies. The present invention provides antibodies comprising an antigen binding region that binds to CD137. The present invention also provides a bispecific antibody comprising a first antigen binding region that binds to CD137 and a second antigen binding region that binds to an immune checkpoint molecule, an immune stimulatory molecule or a tumor antigen. The invention provides pharmaceutical compositions comprising the antibodies and methods of treating cancer.

The invention belongs to the technical field of biological medicines, and particularly discloses a pH and ultrasound double-response type oncolytic microorganism as well as a preparation method and application thereof. On the basis of a tumor targeting platform, a mild thermal response gene loop expression GM-CSF and a surface-coated oncolytic microbial system are integrated, chemotherapeutic drugs are released in a tumor core area, and immunogenic cell death is induced. A thermal response loop is accurately activated through low-intensity focused ultrasound, and engineering bacteria are promoted to express GM-CSF and secrete a large amount of mannose modified OMVs. Due to the nanometer size and mannose targeting of the OMVs, the OMVs are efficiently enriched in lymph nodes, the OMVs are reprogrammed into an immune activation state from an immune tolerance state, and the OMVs and ICD cooperate to promote dendritic cell maturation, tumor antigen presentation and activation of tumor killer T cells, so that a remarkable and powerful treatment effect is achieved in various tumor models, and the application prospect is wide. A new strategy is provided for remodeling the lymph node immune microenvironment and enhancing the anti-tumor immune response.

The present invention addresses the problem of providing a novel treatment method for T-cell tumors that can induce cell damage in tumor cells and can be used in the treatment of a T-cell tumor of a subject with T-cell dysfunction. The present invention provides a therapeutic agent for a T-cell tumor of a subject with T-cell dysfunction, said therapeutic agent comprising a bispecific antigen-binding molecule, wherein the bispecific antigen-binding molecule includes (1) at least one section that specifically binds to a target tumor antigen expressed in T-cell tumor cells, and (2) at least one section that specifically binds to an antigen which is a normal T-cell-side target antigen and has a subtype, provided that the target tumor antigen expressed in T-cell tumor cells is not present in normal T-cells, or if present, the normal T-cells are substantially not activated when the bispecific antigen-binding molecule binds to the antigen that is present in the normal T-cells and is the same as the target tumor antigen, and a sufficient ratio of the subtype of the normal T-cell-side target antigen is present such that the normal T-cells are activated by the bispecific antigen-binding molecule binding to the normal T-cell-side target antigen and a sufficient number of activated T-cells for treatment of the T-cell tumor are provided.

The present invention relates to genetic engineering delivery and use of a tumor antigen peptide fusion protein and a composition thereof. A tumor antigen peptide fusion protein and a composition thereof have immunogenicity, therapeutic efficacy, and specificity.