24 results about "Germinal center" patented technology

The invention relates to the technical field of immunization. The invention discloses parabacteroides dieldrii and parabacteroides goldsteinii, an application of the parabacteroides dieldrii and / or the parabacteroides goldsteinii in preparation of an immunopotentiator of a vaccine, and the immunopotentiator of the vaccine, and particularly discloses the parabacteroides dieldrii and the parabacteroides goldsteinii, the application of the parabacteroides dieldrii and / or the parabacteroides goldsteinii in preparation of the immunopotentiator of the vaccine. The parabacteroides dieldrii and / or the parabacteroides gold can be used as an immunopotentiator, can activate immunity, enhance antibody titer and shorten antibody generation reaction time, and can remarkably promote proliferation of B cells, plasma cells and memory B cell subgroups in a hair growth center.

The present invention relates to glycosylate HIV timer nanoparticles fused to self-assembling ferritin proteins which may be utilized as immunogens to enhance trafficking to lymph nodes and germinal centers and to heighten immune responses.

Described herein is an engineered viral subunit vaccine encoding ASFV capsid proteins (e.g., P72 and Penton) for use in pigs. The vaccine with either P72 or Penton tested in mice elicited significantly higher levels of antigen-specific IgM and IgG, increased frequency of antibody-secreting cells in the bone marrow, and higher quality germinal centers in the spleens of immunized mice. Enhanced T cell responses were also observed, with higher levels of IFN-γ and TNF-α in splenocytes. Immunogenicity assessments in pigs further supported these findings, with both MB-P72 and MB-PN180Q inducing robust B cell and T cell responses. These findings show that expression of capsid proteins P72 and Penton in membrane-bound forms via mRNA preserves their native multimeric structure and enhances their immunogenicity and provides a basis for an effective ASFV vaccine.

The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of lymphoma (e.g., a diffuse large B-cell lymphoma (e.g., a germinal-center B-cell-like or activated B-cell-like diffuse large B-cell lymphoma). The invention is based, at least in part, on the discovery that macrophage biomarkers are useful in methods of identifying, diagnosing, or predicting the therapeutic efficacy of treatment with an anti-CD79b immunoconjugate (e.g., polatuzumab vedotin) and an anti-CD20 antibody (e.g., obinutuzumab or rituximab).

E. coli Nissle 1917 (EcN) engineered to express human chemokine CXCL13 (EcNhCXCL13) for intravesical delivery to treat muscle-invasive bladder cancer and similar disorders.

The application belongs to the technical field of biological preparations, and particularly relates to a manganese-based hydrogel rabies vaccine and a preparation method and application thereof. The manganese-based hydrogel rabies vaccine is based on modified chitosan hydrogel, in which inactivated rabies virus and manganese ions are added. The adjuvant and antigen are co-delivered through injection, slowly dissolve with tissue effusion infiltration, gradually release manganese ions to activate cGAS-STING, enhance the activity of immune cells and stimulate the production of germinal centers. At the same time, the released antigens are processed by immune cells or immune organs to produce antibodies to block viral infection. The manganese-based hydrogel rabies vaccine can significantly improve the duration of antibody action, prolong the antibody protection time, enhance the activity of immune cells and stimulate the production of germinal centers, and improve the antibody production level.

The invention discloses application of an SETD8 inhibitor in preparation of a medicine for treating diffuse large B-cell lymphoma, and belongs to the technical field of biological medicine. The SETD8 inhibitor is preferably UNC0379, and the diffuse large B-cell lymphoma comprises a hair growth center B-cell-like lymphoma and a non-hair growth center B-cell-like lymphoma. The medicine prepared from the SETD8 inhibitor can effectively inhibit proliferation of diffuse large B-cell lymphoma cells, induce apoptosis of the diffuse large B-cell lymphoma cells and inhibit growth of in-vivo diffuse large B-cell lymphoma tumor cells. The invention also provides a pharmaceutical composition for treating diffuse large B-cell lymphoma, which comprises the SETD8 inhibitor as an active component and is supplemented with a pharmaceutically acceptable carrier or auxiliary material. The application range of the SETD8 inhibitor is expanded, a new drug choice is provided for solving the problem that in an existing treatment scheme, drug resistance or relapse of a diffuse large B-cell lymphoma patient is prone to occurring, and the SETD8 inhibitor has important clinical application value.

Provided herein are methods of treating diseases (e.g., proliferative disease (e.g., cancer (e.g., breast cancer, colon cancer, testicular cancer, CNS cancer, stomach cancer, lymphoma (e.g., B-cell lymphoma (e.g., lymphoplasmacytic lymphoma (e.g., IgM secreting lymphoplasmacytic lymphoma (i.e., Waldenstrom's Macroglobulinemia), non-IgM secreting lymphoplasmacytic lymphoma)), diffuse large B-cell lymphoma (e.g., activated B-cell-like (ABC)-DLBCL, germinal center B-cell-like (GBC)-DLBCL), follicular lymphoma, marginal zone B-cell lymphoma, small lymphocytic lymphoma, mantle cell lymphoma), and leukemia (e.g., chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia, myelogenous leukemia (e.g., chronic myelogenous leukemia, acute myelogenous leukemia))))) comprising administering to the subject in need thereof a therapeutically effective amount of Compound (I). Further provided are methods for treating disease resistant to treatment with BTK inhibitors (e.g., ibmtinib). Formula (I)

Developing an effective HIV-1 vaccine is contingent on generating protective antibodies (Abs). Novel antigen delivery methods are needed to enhance immune responses. One promising approach involves directing antigens to dendritic cells (DC) through fused monoclonal antibodies (mAbs) to amplify both cellular and humoral responses. Here, the inventors aimed to refine Langerhans cells (EC) targeting by designing three Env monochains instead of 2 (EC3. Env3) mimicking natural Env conformation. The inventors demonstrated that EC3. Env3 construct (i) elicited a rapid and potent Env-IgG response, (ii) enhanced the avidity of anti-Env IgG that was accompanied by a marked expansion of Tfh and GC B cells and (iii) swiftly induced the formation of structured germinal centers in dLN, indicative of a robust immune response. Finally, significant Tier-1 NeutAb induction was observed in rabbits immunized with the construct. In conclusion, HIV Env antigen can be adaptively targeted to LC as a timer, intensifying both the magnitude and quality of humoral responses. The present invention thus relates to the use of such a construct as LC targeting HIV-1 vaccines.

The invention discloses application of tazeostat in preparation of a medicine for preventing and treating cardiac transplantation chronic rejection, and belongs to the technical field of biological medicine. The medicine reduces the trimethylation level of histone H3 around a B cell p21 gene at a lysine 27 site through epigenetic regulation, relieves epigenetic inhibition on the p21 gene to highly express p21 molecules, influences differentiation of the B cell to a hair growth center B cell and plasma cells, and further relieves antibody-mediated rejection reaction, so that the survival time of a graft is remarkably prolonged, and the survival rate of the graft is improved. The function of the transplanted heart is improved.

The application discloses a hepatitis B surface antigen specific B cell receptor gene knock-in mouse model, and establishes a hepatitis B virus surface antigen (HBsAg) specific B cell receptor (BCR) gene knock-in mouse model, wherein 70-90% of B cells of the mouse can specifically recognize HBsAg, and differentiate into germinal center B cells and plasma cells. Therefore, the model can be used for basic research on hepatitis B antiviral humoral immune response and tolerance mechanism, and can also be used for application research on development of drugs and vaccines for breaking HBsAg immune tolerance. In summary, the establishment of the model lays a solid foundation for development of a functional cure immune means for hepatitis B.

The application discloses a use of ursolic acid as a SARS-CoV-2 subunit vaccine adjuvant, aims to solve the technical problems of relatively weak immunogenicity of existing subunit vaccines, possible local or systemic adverse reactions of some adjuvants and unclear action mechanism, and provides a new medical use of ursolic acid. The ursolic acid can effectively improve the antigen-specific antibody level of the subunit vaccine immunized mice, promote the formation of germinal centers and enhance follicular helper T cell response. The action mechanism is that after the ursolic acid is combined with PTPRF, the stability of the PTPRF is affected and the degradation of the PTPRF is promoted, thereby enhancing the downstream STAT3 phosphorylation, promoting the expression of antigen presentation related genes and improving the antigen presentation ability of the dendritic cells, and finally enhancing the antibody response of the body. The application provides a new subunit vaccine adjuvant candidate molecule for preventing severe SARS-CoV-2 related infections in clinic, and provides a new molecular target and mechanism basis for the development of subunit vaccine adjuvants.

The invention provides a three-level lymph structure spatial heterogeneity-based tumor prognosis evaluation method and system. The evaluation method comprises the following steps: S1, obtaining a tumor tissue Hamp; e, dyeing the section, and generating a full-section image through digital scanning; s2, identifying a T region and a P region in the full-slice image; s3, marking contour boundaries and GC regions of all TLSs on the full slice image, and counting the hair growth center area ratio GTR of each TLS, GTR = (GC area / TLS area) * 100%; s4, calculating the GTR arithmetic mean value of all the TLSs in the T region as a T score, and calculating the GTR arithmetic mean value of all the TLSs in the P region as a P score; and S5, generating a composite M score through a formula M = 0.777 * T score-0.443 * P score. According to the tumor prognosis evaluation method based on the spatial heterogeneity of the three-level lymphatic structure, only conventional Hamp is needed; the complex immunohistochemistry is replaced, the detection cost is reduced, the detection period is shortened, and the limitation that TLS is regarded as a homogeneous structure in the prior art is broken through.

This application discloses an application of a functional organ typing system based on human immune organoids in rheumatoid arthritis (RA), relating to the field of biomedical technology. This application develops a functional organ typing system based on human immune organoids. Using this model, the in vivo immune imbalance characteristics of RA are successfully reproduced. The in vitro state of T and B lymphocytes in RA patients is simulated, including germinal center formation, autoantibody secretion, inflammatory cytokine production, and immune cell interactions. Establishing such organoid models helps to more comprehensively elucidate the pathogenesis of rheumatoid arthritis and identify novel therapeutic targets associated with these immune cell populations.

This invention discloses a neutralizing nucleic acid aptamer that targets and inhibits B-cell activating factors and its application in the treatment of systemic lupus erythematosus (SLE). The neutralizing nucleic acid aptamer described in this invention can efficiently inhibit the binding of BAFF to specific receptors on the B-cell membrane, including the BAFF receptor (BAFF-R), human calmotropic cyclin ligand-interacting molecule (TACI), and B-cell maturation antigen (BCMA), thereby reducing the proportion of plasma cells, plasmablasts, and germinal center B cells, ultimately reducing the production and secretion of autoantibodies, thus exhibiting a targeted therapeutic effect on SLE. Compared with existing BAFF-neutralizing biological agents, the neutralizing nucleic acid aptamer of this invention has advantages such as high specificity, high affinity, ease of synthesis, low immunogenicity, low cost, and designability and programmability, making it a potential novel nucleic acid agent for targeted SLE therapy with excellent prospects for clinical translational applications.

The invention relates to an emulsion with long-acting immune response and a preparation method and application thereof, the emulsion comprises a water phase, an oil phase and particles, the water phase comprises an inner water phase and an outer water phase, the inner water phase contains the particles, the oil phase wraps the inner water phase, and the outer water phase wraps the oil phase. According to the emulsion provided by the invention, the particles are introduced into the emulsion, the deformability of the emulsion and the bionic characteristics of the particles are utilized, cellular uptake and efficient lymph node enrichment are remarkably enhanced, rapid and powerful hair growth center reaction is induced, a body can be induced to generate strong cellular and humoral immune response on a mouse model, and a protective antibody is continuously generated.

The invention relates to an emulsion for low-response or non-response people and a preparation method and application thereof, the emulsion comprises a water phase, an oil phase and particles, the water phase comprises an inner water phase and an outer water phase, the inner water phase contains the particles, the oil phase wraps the inner water phase, the outer water phase wraps the oil phase, and the oil phase is provided with a cavity. The emulsion adjuvant provided by the invention remarkably improves the immune response effect of individuals, especially the elderly, promotes the uptake of cells to antigens by utilizing the structural variability of the emulsion, and improves the bioavailability of the antigens by efficiently loading the antigens in the aqueous phase of the emulsion, thereby inducing rapid and powerful hair growth center reaction, and improving the development of the hair growth center. The aims of improving the immune cell activity and improving the vaccine response efficiency are fulfilled.

The invention relates to the technical field of biological medicines, and particularly discloses an organoid simulating a lymphatic epithelial tissue structure and application thereof. The organoid comprises an immune micro-region capable of supporting B cell activation, somatic mutation and / or the formation of a hair growth center-like structure, and the organoid is derived from a cell population of lymph-related tissue. According to the method, a Transwell three-dimensional culture system supported by a low-concentration matrix is adopted, and optimized culture conditions are combined, so that B cells are promoted to form a hair growth center-like structure in an organoid. The method can be applied to mucosal immune mechanism research, vaccine or immunologic adjuvant evaluation, immunomodulatory drug screening, antibody discovery and screening, hair growth center related immune response research and the like.

The invention provides a fusion gene and an HPV nucleic acid vaccine. A fusion gene is obtained through research and optimization, and the fusion gene is obtained by sequentially connecting an L1 gene of an HPV 16 type, an E5 gene, an E6 gene and an E7 gene of the HPV 16 type and an E5 gene, an E6 gene and an E7 gene of an HPV 52 type. The inventor finds that an HPV vaccine prepared by taking the fusion gene as an antigen component can effectively promote cellular immune response and formation of long-term protective memory, promote hair growth center response and formation of humoral immune memory, remarkably improve the proportion of NKT cells, successfully activate systemic anti-tumor cell immune response of mice, and improve the anti-tumor effect of the mice. The anti-tumor immune effect is greatly improved. The traditional Chinese medicine composition has the dual effects of prevention and treatment, has the prevention capability, can effectively inhibit tumor growth and has the tumor treatment capability. The HPV vaccine also has the advantages of high safety, good stability and the like, and has a wide application prospect.

Compounds and methods for treatment of cancers such as multiple myeloma by inhibition of germinal center kinase.

The present invention provides diagnostic methods, therapeutic methods, and therapeutic compositions for lymphoma (e.g., diffuse large B-cell lymphoma (e.g., hair center B-cell-like or activated B-cell-like diffuse large B-cell lymphoma). The present invention is based, at least in part, on the discovery that macrophage biomarkers can be used in methods for identifying, diagnosing, or predicting the efficacy of treatment with an anti-CD79b immunoconjugate (e.g., vipostuzumab) and an anti-CD20 antibody (e.g., ototuzumab or rituximab).

Described herein is an engineered viral subunit vaccine encoding ASFV capsid proteins (e.g., P72 and Penton) for use in pigs. The vaccine with either P72 or Penton tested in mice elicited significantly higher levels of antigen-specific IgM and IgG, increased frequency of antibody-secreting cells in the bone marrow, and higher quality germinal centers in the spleens of immunized mice. Enhanced T cell responses were also observed, with higher levels of IFN-γ and TNF-α in splenocytes. Immunogenicity assessments in pigs further supported these findings, with both MB-P72 and MB-PN180Q inducing robust B cell and T cell responses. These findings show that expression of capsid proteins P72 and Penton in membrane-bound forms via mRNA preserves their native multimeric structure and enhances their immunogenicity and provides a basis for an effective ASFV vaccine.

The present invention relates to an immunologic adjuvant comprising poly (beta-hydroxybutyrate) nanoparticles, and a vaccine composition comprising the poly (beta-hydroxybutyrate) nanoparticles. The nanoparticles based on the non-cytotoxicity and obtaining the FDA approved substance not only have no cytotoxicity and high biosafety, but also can make up for the disadvantages of BHB. Unlike existing commercialized immunologic adjuvants, the present invention is a novel nanoscale immunologic adjuvant based on a substance derived from a living body, which is versatile with respect to antigens having a protein form, not limited to specific antigens, and has the convenience of being able to function in the form of a single mixture. Furthermore, the present invention can also be used as a base material for a next-generation immunologic adjuvant, which effectively enhances humoral immunity and cellular immunity at the same time by functionally increasing the activity of antigen presenting cells (APC) and by inducing the activity of follicular helper T cells (follicular helper T cells) and the activity of germinal center B cells (germinal center B cells).

The invention discloses an application of a benzoylguanidine derivative in preparation of a medicine for treating and / or preventing chronic inflammatory diseases. According to the invention, the benzoylguanidine derivative is prepared into a hydrogel dosage form, and the hydrogel dosage form acts on a psoriasis affected part in a smearing manner, so that psoriasis-like skin lesion symptoms such as skin scales, erythema and epidermis thickening can be relieved, skin inflammatory cell infiltration and epidermis thickness can be relieved, spleen inflammatory cell infiltration can be relieved, and abnormal activity of a hair growth center can be improved; the traditional Chinese medicine composition reduces inflammatory reactions such as spleen index, reduces the level of inflammatory factors in plasma and spleen, and shows a good psoriasis treatment effect. Therefore, the benzoylguanidine derivative and the hydrogel preparation thereof have the remarkable advantages of safety, few toxic and side effects and no pollution of drug residues, and have a remarkable treatment effect and potential for realizing medical transformation.