83 results about "Tumor-specific antigen" patented technology

The present disclosure relates to methods of diagnosing or treating bone marrow disorders and acute leukemia by using a tumor-specific antigen selected from the group consisting of CD63, CD151, CD72, CD84, CD69 and CD109. Antigen binding proteins (ABPs), ABP-drug conjugates, and CARs targeting tumor specific antigens are also provided, as are methods of their use.

The invention relates to a preparation method of a tumor microenvironment response type nano drug delivery system, which comprises the following steps: forming MnO2 nanoclusters through biomineralization induction under an alkaline condition, modifying HSA nanoparticles, then loading Ce6 through a carbodiimide method, and finally combining with a PD-L1 antibody by adopting a copper-free click chemistry method to obtain nanoparticles HMC and anti-PD-L1. The nanoparticle can be retained in a tumor tissue in a passive targeting manner through an EPR effect, and is decomposed into Mn < 2 + >, O2 and a small molecule drug through a high H2O2 and low pH microenvironment of the tumor tissue, so that the tumor permeability is greatly enhanced, the tumor immunogenicity is enhanced by combining sonodynamic therapy, the release of a tumor specific antigen and the aging of antigen presenting cells are promoted, and the tumor treatment effect is enhanced. The infiltration of tumor T cells is increased, and cold tumors are changed into hot tumors; the nanoparticles can generate O2 in situ at the same time, and the immunosuppressive ability and drug resistance caused by tumor hypoxia are overcome.

The present invention discloses an enhanced tumor vaccine adjuvant, and specifically relates to the field of vaccine adjuvants, the adjuvant comprising granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-2 (IL-2), interleukin-9 (IL-9), gamma interferon (IFN-γ) and at least one additional immunomodulatory factor, wherein the immunomodulatory factor is selected from tumor-specific antigen WT1, CD40 ligand (CD40L), Toll-like receptor agonist or a combination thereof. The tumor vaccine adjuvant of the present invention can enhance the body's immune response to the tumor vaccine and improve the prevention and treatment effect of the tumor vaccine on tumors.

The present disclosure provides a composition comprising a nucleic acid sequence encoding from about 1 to about 100 amino acid sequences, the amino acid sequences being tumor-specific antigens wherein at least one tumor-specific antigen is an amino acid sequence associated with the WNT pathway. In some embodiments, the nucleic acid sequence encodes from about 20 to about 60 tumor specific antigens; wherein from about 1 to about 8 tumor specific antigens are selected from one or a combination of the following: WNT, CTNNB1, AXIN1, AXIN2, APC, CK1, and GSK3B. Also provided is a cell comprising any one or more compositions disclosed herein and a pharmaceutical composition comprising: (i) a therapeutically effective amount of one or more compositions as disclosed herein; and (ii) a pharmaceutically acceptable carrier. A method of treating cancer in a subject in need thereof is also provided.

Colorectal cancer (CRC) has not benefited from innovative immunotherapies, mainly because of the lack of actionable immune targets. Novel tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs) expressed by CRC cells are described herein. Most of the TSAs described herein derives from aberrantly expressed unmutated genomic sequences, such as intronic and intergenic sequences, which are not expressed in normal tissues. Nucleic acids, compositions, cells, antibodies and vaccines derived from these TSAs are described. The use of the TSAs, nucleic acids, compositions, antibodies, cells and vaccines for the treatment of CRC is also described.

The present disclosure relates to compositions and methods of killing cells in vitro or in vivo. In particular examples, the method includes contacting a cell having a cell surface protein with a therapeutically effective amount of an antibody-IR700 molecule, wherein the antibody specifically binds to the cell surface protein. In particular examples the antibody recognizes a tumor-specific antigen on the surface of a tumor cell. The cell is subsequently irradiated, such as at a wavelength of 660 to 740 nm at a dose of at least 1 J cm−2, thereby killing the cell. Also provided are wearable devices that include an article of clothing, jewelry, or covering; and an NIR LED incorporated into the article, which can be used with the disclosed methods.

Provided are a chimeric antigen receptor, and a GPRC5D antibody-containing chimeric antigen receptor and a use thereof. The chimeric antigen receptor comprises: an extracellular domain, wherein the extracellular domain is capable of binding to a tumor antigen; a transmembrane domain, wherein the transmembrane domain is connected to the extracellular domain, and the transmembrane domain is derived from an I-type transmembrane protein or an artificially synthesized transmembrane protein having a hydrophobic helix; and an intracellular domain, wherein the intracellular domain is connected to the transmembrane domain, and the tumor antigen is a tumor-specific antigen or a tumor-associated antigen. The amino acid sequence of the transmembrane domain is optimized, thereby providing a GPRC5D antibody-containing chimeric antigen receptor and engineered immune cells; and the engineered immune cells obtained on the basis of the GPRC5D antibody have specific killing performance on multiple myeloma.

The invention relates to the technical field of biology, in particular to a chimeric antigen receptor, a chimeric antigen receptor containing a GPRC5D antibody and application of the chimeric antigen receptor, and the chimeric antigen receptor comprises an extracellular domain which can be combined with a tumor antigen, an inflammatory factor or a pathogen antigen; the transmembrane domain is connected with the extracellular domain, and the transmembrane domain is derived from a type I transmembrane protein or an artificially synthesized transmembrane protein with a hydrophobic helix; the intracellular domain is connected with the transmembrane domain, and the tumor antigen is a tumor specific antigen or a tumor associated antigen. The inventor optimizes the amino acid sequence of the transmembrane domain, so that the chimeric antigen receptor containing the GPRC5D antibody and the engineered immune cell are provided, and the engineered immune cell obtained based on the GPRC5D antibody has specific killing performance on multiple myeloma.

Breast cancer is now the most common cancer in the world, and despite treatment progression in decades in the past, metastatic breast cancer is still a disease which cannot be cured. Novel tumor specific antigens (TSA) and tumor associated antigens (TAA) expressed by breast tumor cells are described herein. Synthetic long peptides, nucleic acids, compositions, cells, TCRs, antibodies, and vaccines derived from these TSAs and TAAs are described. The use of the TSA / TAAs, nucleic acids, compositions, antibodies, cells and vaccines for the prevention or treatment of breast cancer, including triple negative breast cancer (TNBC), is also described.

The application provides a kind of nanoparticle, preparation method and its early screening related application of cancer, wherein, nanoparticle includes superparamagnetic nanometer core, cationic polymer modified on the surface of superparamagnetic nanometer core and targeted polypeptide grafted on cationic polymer, the targeted polypeptide can specifically recognize tumor specific antigen protein, and has the modular structure of rigid helix and charge repulsion sequence.The plasma low-abundance protein enrichment nanoparticle provided by the application can be used for the detection of early screening of tumor through liquid biopsy, can significantly improve the detection rate of early tumor, and has important clinical significance.

The present invention provides an RNA-based tumor vaccine, a preparation method, an immune adjuvant, a vector and an application. The tumor vaccine can specifically act on tumors with positive expression of GPC3, such as hepatocellular carcinoma, ovarian clear cell carcinoma, yolk sac carcinoma, etc. The tumor vaccine includes circular RNA capable of encoding an immunogenic polypeptide. The circular RNA is configured to be capable of specifically encoding the immunogenic polypeptide GPC3. The circ-GPC3 in the present invention has a covalently closed-loop structure that can protect it from exonuclease-mediated degradation, has a longer half-life and higher stability compared to mRNA, and can ensure the continuous expression of immunogenic proteins. By artificially modifying and introducing a ribosome entry site (IRES) modification, the present invention can increase the translation efficiency of tumor-specific antigen RNA.

The invention discloses a method and a pharmaceutical composition for inhibiting tumor growth by combining an mRNA vaccine and a transforming growth factor-beta (TGF-beta) antibody. The medicine composition comprises an mRNA vaccine for coding a tumor specific antigen and a monoclonal antibody for specifically targeting TGF-beta, and tumor specific immune response induced by the mRNA vaccine is combined with the effect of the TGF-beta antibody for relieving tumor microenvironment immunosuppression, so that the killing ability of a body to tumor cells is remarkably enhanced; the compound provided by the invention can effectively inhibit tumor growth and prolong the lifetime of tumor-bearing individuals, has good safety and tolerance, and provides a new effective strategy for tumor treatment.

The invention provides a nanoparticle, a preparation method and a cancer early screening related application thereof, the nanoparticle comprises a superparamagnetic nano core, a cationic polymer modified on the surface of the superparamagnetic nano core and a targeting polypeptide grafted on the cationic polymer, the targeting polypeptide can specifically recognize a tumor specific antigen protein, and has a modular structure comprising a rigid helix and a charge repulsion sequence. The plasma low-abundance protein-enriched nanoparticles provided by the invention can be used for early screening detection of tumors through liquid biopsy, can significantly improve the detection rate of early tumors, and have important clinical significance.

To provide an allogeneic tumor cell vaccine.SOLUTION: Provided is an allogeneic tumor cell vaccine, comprising: (1) a population of proliferation-incompetent, live, genetically engineered tumor cells expressing one or more tumor-specific antigens, the population comprising at least three stably expressed immunomodulatory molecules, at least three immunomodulatory molecules being OX40 ligand (OX40L), CD27 ligand (CD70), and CD28 ligand (CD28L) including CD80, CD86, or both, to induce one or more subpopulations of PBMCs to proliferate in response to the expressed immunomodulatory molecules and subsequently enter an effector phase to kill tumor cells, and the subpopulations of PBMC cells comprising one or more of T lymphocytes, natural killer (NK) cells, dendritic cells (DCs), or B lymphocytes; and (2) a pharmaceutically acceptable carrier.SELECTED DRAWING: None

This invention discloses a method for inducing B-CD4 + Freeze-dried tumor tissue with T-cell interaction, its preparation method, and its applications. This study aims to address the lack of effective treatments for postoperative recurrence of microsatellite stable (MSS) solid tumors, the easy degradation and inactivation of traditional autologous whole antigen vaccines, insufficient presentation efficiency, and the limitation of only activating classical CD8. + The core bottleneck of the T cell pathway. This invention utilizes vacuum freeze-drying technology to prepare porous, degradable freeze-dried tumor tissue (LT) from clinically derived or artificially cultured tumor tissue. This process fully preserves the tumor's complete antigen spectrum, tumor-specific antigens, and the immunogenicity of related antigens. It allows for highly efficient antigen presentation via dendritic cells, specifically inducing B cells and CD4+. + T-cell interaction mediates non-classical anti-tumor immunity that does not rely on traditional cytotoxic immune cells, significantly inhibiting the growth of residual lesions after solid tumor surgery. It has both broad-spectrum anti-cancer effects and excellent biosafety, and is especially suitable for postoperative adjuvant immunotherapy for MSS-type colorectal cancer.

The present patent application relates to nanoparticles for the delivery and targeting of a non-tumour-specific antigen in cancer cells, comprising a matrix support based on a biocompatible material, the non-tumour-specific antigen, and an adjuvant, for use in recalling, in cancer patients who have a specific immunity for the non-tumour- specific antigen pre-existing to the tumour pathology, the immune response specific to the non-tumour-specific antigen against the cancer cells. A further object of the application is anti-tumour pharmaceutical formulations comprising nanoparticles and kits comprising the aforementioned anti-tumour pharmaceutical formulations in combination with traditional anti-tumour vaccines.

The present invention relates to the use of an antibody or an immunologically active fragment thereof, which specifically binds to integrin β2, as an immuno-oncology agent. The chimeric and humanized antibodies of the present invention specifically bind to integrin β2, which is a tumor-specific antigen and is expressed on the cell membrane of M2 tumor-associated macrophages, and thus can be used as an antibody therapeutic agent for cancer treatment using a cancer cell death mechanism by immune cell activation, an antibody therapeutic agent for cancer treatment, or a cell therapeutic agent for cancer treatment, and can also be used for cancer diagnosis.

The invention discloses application of a toxoplasma gondii gene deletion strain for expressing a tumor specific antigen receptor in preparation of an anti-tumor biological preparation. The toxoplasma gondii gene deletion strain (CAR-Tg) for expressing a tumor specific antigen receptor is used for resisting tumors, and particularly, the thought and strategy for treating solid tumors have obvious advantages and innovations, so that the toxoplasma gondii gene deletion strain is a positive application for resisting tumors of toxoplasma gondii; compared with a CAR-T therapy method, the CAR-Tg strain for anti-tumor therapy can effectively overcome the defects that the treatment effects of individualized customization, time and labor waste, insufficient T cell infiltration, depletion and the like are limited, potential carcinogenic risks exist and the like, and has remarkable gain and effects; the CAR-Tg strain expresses a tumor specific antigen receptor on the basis of a toxoplasma gondii gene deletion strain, the targeted tumor killing capacity of toxoplasma gondii can be improved, the anti-tumor effect is improved, and the anti-tumor effect can be improved when the CAR-Tg strain is combined with an anti-tumor drug such as a small-molecule inhibitor.

Disclosed are methods of treating or preventing cancer in a mammal, the method comprising: (a) isolating T cells from a tumor sample from the mammal, wherein the isolated T cells are one or both of exhausted and differentiated, and the isolated T cells have antigenic specificity for a tumor-specific antigen expressed by the tumor sample from the mammal, wherein the tumor-specific antigen is a tumor-specific neoantigen or an antigen with a tumor-specific driver mutation; and optionally expanding the numbers of isolated, tumor antigen-specific T cells; and (b) administering to the mammal (i) the isolated T cells of (a) and (ii) a vaccine which specifically stimulates an immune response against the tumor-specific antigen for which the isolated T cells have antigenic specificity.

The application discloses a recombinant adenovirus vector tumor vaccine and a preparation method and application thereof, wherein the antigen coded by the recombinant adenovirus vector tumor vaccine comprises any one or a combination of more than two antigen peptide epitopes of KRAS protein. The recombinant adenovirus vector tumor vaccine of the application codes multiple KRAS tumor-specific antigen peptides, and has a good killing effect on KRAS mutation-driven tumors, especially lung tumors. The vaccine can be inhaled in a form of atomization, injected into muscles first and then inhaled in a form of atomization, inhaled in a form of atomization first and then injected into muscles, injected into muscles, or simultaneously injected into muscles and administered in a form of atomization. After atomization, the vaccine can be inhaled through a nasal cavity or an oral cavity to reach the lungs, generate an anti-tumor protective immune response on the respiratory tract, the lungs and the whole body, and enhance the utilization rate and the treatment effect of the vaccine.

The present disclosure provides a universal mRNA tumor vaccine and a preparation method and use thereof. The universal mRNA tumor vaccine is constructed based on a concatemer antigen peptide, and comprises a combined peptide segment containing at least two tumor-specific antigen peptides and tumor-associated antigen peptides. The concatemer antigen peptide provided by the present disclosure comprises a plurality of immunogenic antigens. The mRNA tumor vaccine constructed based thereon has good antigen expression efficiency in cells and can produce strong cellular immune effects, and can be used for treating and / or preventing tumors (e.g., colorectal cancer), and can also be combined with other anti-tumor drugs (e.g., anti-PD-1 antibodies) for treating tumors (e.g., colorectal cancer).

The invention provides a lactic acid response type promoter which comprises a lactic acid response core element, and the lactic acid response core element comprises a sequence as shown in SEQ ID NO: 1, or the lactic acid response core element is as shown in SEQ ID NO: 1. The invention also provides an expression cassette containing the lactic acid responsive promoter, a recombinant vector and a host cell. The lactic acid response type promoter can respond to lactic acid in a tumor microenvironment, so that off-target toxicity caused by lack of tumor specific antigens is greatly reduced, and the treatment specificity on tumor focuses is improved.

To provide novel tumor-specific antigens (TSAs), since ovarian cancer, notably high-grade serous ovarian cancer (HGSC), the principal cause of death from gynecological malignancies in the world, has not significantly benefited from recent progress in cancer immunotherapy and the nature of antigens that can elicit anti-HGSC immune responses is unknown while HGSC infiltration by lymphocytes correlates with superior survival.SOLUTION: Novel tumor-specific antigens (TSAs) shared by a large proportion of ovarian tumors are described herein. Most of the TSAs (>80%) described herein derives 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 TSAs are described. Use of the TSAs, nucleic acids, compositions, cells and vaccines for treatment of ovarian cancer is also described.SELECTED DRAWING: Figure 6A

Breast cancer is now the most prevalent cancer worldwide, and despite therapeutical advances in the last decades, metastatic breast cancer remains an incurable disease. Novel tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs) expressed by breast tumor cells are described herein. Synthetic long peptides, nucleic acids, compositions, cells, TCRs, antibodies and vaccines derived from these TSAs and TAAs are described. The use of the TSAs / TAAs, nucleic acids, compositions, antibodies, cells and vaccines for the prevention or treatment of breast cancer, including triple-negative breast cancer (TNBC), is also described.

Ovarian cancer, notably high-grade serous ovarian cancer (HGSC), the principal cause of death from gynecological malignancies in the world, has not significantly benefited from recent progress in cancer immunotherapy. While HGSC infiltration by lymphocytes correlates with superior survival, the nature of antigens that can elicit anti-HGSC immune responses is unknown. Novel tumor-specific antigens (TSAs) shared by a large proportion of ovarian tumors are described herein. Most of the TSAs (>80%) described herein derives 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 TSAs are described. The use of the TSAs, nucleic acids, compositions, cells and vaccines for the treatment of ovarian cancer is also described.

The present invention relates to compositions and methods for generating a nucleic acid delivery system comprising a nucleic acid sequence encoding a heterologous protein comprising a canine tumor-specific antigen (canine melanoma polyepitope (K9Melapoly)) and an inhibitor of an immuno-inhibitory pathway (HSV-1 gD). Additionally, the current invention includes compositions and methods of treating and / or preventing or immunizing a canine against melanoma, and methods of inducing an effector and memory T cell immune response in a canine administered the nucleic acid delivery system of the invention. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a canine as well as a protein expression system.

The present invention relates to a FLT3L–flagellin hybrid adjuvant with enhanced antigen cross-presentation efficacy and a vaccine composition comprising same. The hybrid adjuvant of the present invention demonstrated significant therapeutic efficacy as an adjuvant for a therapeutic cancer vaccine in a preclinical mouse model of cervical cancer, resulting in complete tumor regression and sustained protection. In addition, the hybrid adjuvant of the present invention induced tumor-specific antigen CD8+ T cell responses and progenitor-exhausted CD8+ T cells (Tpex) due to an increase in cross-presentation by conventional type 1 dendritic cells (cDC1) in tumor-draining lymph nodes and the tumor microenvironment, and the combination of TCV having the hybrid adjuvant applied thereto and anti-PD-1 therapy significantly improves survival outcomes in anti-PD-1–resistant tumors, and thus can be advantageously applied in anticancer immunotherapy using therapeutic cancer vaccines.

In the present invention, the inventors reveal that noncoding RNA, a known source of noncanonical peptides (also called dark matter) and tumour-specific antigens, can shape the precancer immune contexture and are associated with polyp and cancer risk. Through the multimodal characterisation of a unique dataset of 135 well-annotated cancer and precancer lesions from patients developing polyps at low and high frequency, the inventors identified high expression of noncoding RNAs, as a major differentiator of polyp development rate. Noncoding RNAs were also associated with increased immunogenicity associated with increased mature tertiary lymphoid structures within the microenvironment of pre-cancer lesion, higher quantity and quality of adaptive immune cells, including B- and T-cells. Thus, the inventors propose that early carcinogenesis is shaped by noncoding RNA expression and immune microenvironment. These compelling findings reveal potential early biomarkers and targets for prophylactic immune modulation approaches in individuals at high risk of developing colorectal cancer.

Provided herein are examples of mRNA treatment nanoparticles and methods of using them to treat a patient. An mRNA treatment nanoparticle may include one or more mRNAs encoding a tumor-specific antigen and an immunomodulatory agent; and a delivery vehicle molecule encapsulating the one or more mRNAs.