330 results about "Cellular immunity" patented technology

The invention belongs to the technical field of kidney histopathology and immunological evaluation, and particularly relates to a kidney pathology detection kit, a detection method and application, the detection kit comprises 37 rare metal element labeled monoclonal antibodies combined with antigens of in-situ tissue cells, and the detection method comprises the following steps: (1) collecting a sample to be detected, preparing a pre-dyed paraffin section; (2) mixing 37 monoclonal antibodies labeled by rare metal elements, and carrying out antibody staining on various antigen targets on the surfaces of cells in the in-situ tissue; (3) carrying out nucleus DNA staining on the stained tissue sample; and (4) detecting the stained tissue sample through an imaging mass spectrum flow system, and collecting original information data through laser spot firing. The method is an analysis method for fine grouping identification and relative quantification of structural cells, immune cells and pathological injury cells in the clinical nephropathy sample in-situ tissue. And auxiliary diagnosis information is provided for diagnosis, grading, treatment and prognosis detection of various clinical nephropathy.

The invention relates to the technical field of cellular immunotherapy, in particular to application of efonidipine in preparation of a dendritic cell immunologic adjuvant. The invention provides an application of efonidipine in preparation of a dendritic cell immunologic adjuvant. It is found that efonidipine can promote maturation, migration and antigen presentation functions of DCs, and the homing ability of DCs and CD8 + T cell activation are remarkably improved. The activation aspect of efonidipine on DCs comprises improvement of expression of maturation indexes CD80, CD40 and CD86, expression of a migration index CCR7, activation of CD8 + T cells by antigen presentation and the like. The efonidipine used in the invention is a drug approved by FDA for clinical treatment of cardiovascular diseases, the application of the efonidipine in immunotherapy is found, new use of old drugs is realized, and the efonidipine has great economic value.

The invention discloses an artificial antigen presenting cell for efficiently preparing a chimeric antigen receptor T cell (CAR-T) and a construction method of the artificial antigen presenting cell, and belongs to the field of cell therapy and immunotherapy, the artificial antigen presenting cell takes a K562 cell as a platform, an anti-CD3 single-chain antibody, an anti-CD28 single-chain antibody, a membrane binding type cell factor and a costimulatory ligand are stably expressed through genetic engineering, and the chimeric antigen receptor T cell (CAR-T) is obtained. And the local concentration of the anti-CD3 antibody is improved by adopting an HOTag3 tool. The multi-signal integration strategy obviously enhances the activation and proliferation capacity of the T cells, promotes the CAR-T cells to maintain a low differentiation state, and endows the CAR-T cells with excellent anti-tumor activity and durability. The artificial antigen presenting cell provides a novel efficient tool for the field of cellular immunotherapy, and is expected to promote development of more efficient and safer CAR-T therapy to cope with challenges of various malignant tumors.

The invention relates to the technical field of immune carrier microspheres, in particular to an immune carrier microsphere constructed by individualized MHC-II combined polypeptide, a vaccine and application of the immune carrier microsphere and the vaccine. A core comprises microspheres constructed by a plurality of MHC-II binding polypeptides, sequences of the MHC-II binding polypeptides are obtained based on HLA gene typing results of an inoculator, and each HLA gene corresponds to at least one high-affinity MHC-II binding polypeptide; a shell is a glucan with sulfydryl or other polymer coating layer, and sulfydryl is used as a coupling group to be connected with an antigen to construct the vaccine. The method has the advantages that competition is avoided, inhibition is generated, a better immune effect is achieved, antibodies of high-titer carrier molecules are not generated, and cross reaction side effects are avoided. The carrier molecular diversity is reduced; side effects are avoided. And antibody immunity and cellular immunity functions are generated. The particle size of the microspheres is controllable, and the immunologic function can be achieved without adjuvants. The preparation process is simple to operate and good in repeatability.

The invention discloses a nano-carrier based on charge crosslinking, a preparation method of the nano-carrier and application of the nano-carrier as a tumor chemotherapy drug. Wherein the nano-carrier is formed by assembling two polymer chains with positive and negative charges through electrostatic interaction, a precursor ligand on a polymer chain B releases an organic ligand under exogenous or endogenous stimulation, and competes for metal ions on a polymer chain A with positive charges to generate a metal complex in situ, and meanwhile, the electrostatic interaction of the nano-carrier is weakened, so that the metal complex is formed. The dissociation of the nano-carrier is caused, a macromolecular chain B containing an organic ligand is released, and the effect of tumor chemotherapy or immunoregulation is achieved. The method is simple to operate, short in time consumption and mild in reaction condition; the material is good in biocompatibility and high in safety degree. Pharmacodynamic experiments in some embodiments show that the nano-carrier can effectively kill the breast cancer and trigger cellular immunogenic death, meanwhile, tumor cell metastasis is inhibited, and a new thought and means are provided for the clinical problem of breast cancer lung metastasis urgently needing to be solved at present.

The invention discloses a preparation method and application of porcine pseudorabies virus multi-epitope polypeptide, and belongs to the technical field of veterinary biological products. The multi-epitope polypeptide comprises a cytotoxic T cell epitope, a helper T cell epitope and a linear B cell epitope; the cell epitopes are screened from key immunogenic proteins of the pseudorabies virus by using an immunoinformatics method. The porcine pseudorabies virus multi-epitope polypeptide designed by the invention is high in safety, has better antigenicity and physicochemical properties, can be efficiently expressed, and can be recognized by a pseudorabies virus specific antibody. By applying the porcine pseudorabies virus multi-epitope polypeptide, high-level specific antibodies and cellular immune response can be continuously induced to generate, strong protective efficacy is generated, and mice can be protected from death when infected with a lethal dose of porcine pseudorabies virus. Therefore, the multi-epitope polypeptide disclosed by the invention can be used as an alternative antigen of a porcine pseudorabies virus vaccine, the use of active virus is avoided, and a tool is provided for eradication of porcine pseudorabies virus.

The invention relates to the field of medical detection, and particularly provides a diagnostic model for predicting prognosis of gastric cancer CAR-T cellular immunotherapy and application of the diagnostic model. According to the present invention, the content and the spatial distribution map of the CLDN18.2 positive gastric cancer tissue sample microenvironment component are systematically analyzed by integrating the multiple fluorescence immunohistochemical detection and the full-slice digital imaging quantitative analysis method for the first time; through multi-dimensional evaluation of a tumor microenvironment under the treatment background of a targeted CLDN18.2 chimeric antigen receptor T cell immunotherapy CT041, a diagnosis model for predicting the prognosis of the gastric cancer CAR-T cell immunotherapy is established for the first time, accurate screening of benefited people and risk stratification before treatment are realized, treatment selection is guided, and the treatment effect is improved.

The invention provides a plant lactobacillus pentosus for promoting cellular immunoregulation as well as application and a product thereof, and belongs to the field of microorganisms. The preservation number of the provided lactobacillus pentosus is CGMCC (China General Microbiological Culture Collection Center) No.32858, and the lactobacillus pentosus is preserved in the China General Microbiological Culture Collection Center on November 29, 2024. The strain provided by the invention can promote macrophages to secrete TNF-alpha, IL-10 and IL-1beta in a normal state and down-regulate the secretion of NO, and meanwhile, the thermally inactivated strain also has the effect of promoting the macrophages to secrete TNF-alpha, and can further intervene in the secretion of TNF-alpha, IL-10 and IL-1beta in a macrophage inflammation state; in a Caco-2 cell-macrophage co-culture system and a mouse primary epithelial cell-splenic lymphocyte co-culture system, a promotion effect is also shown.

The invention discloses an echinococcosis mRNA (messenger Ribonucleic Acid) vaccine as well as a preparation method and application thereof. The preparation method of the mRNA vaccine for the echinococcosis comprises the following steps: carrying out codon optimization on a modified target antigen protein, then assembling the modified target antigen protein with 5 'UTR, 3' UTR and Poly (A) tail, carrying out gene synthesis, then cloning the synthesized gene into a pUC57 plasmid, and sequentially carrying out plasmid linearization, in-vitro transcription and purification on the constructed recombinant plasmid to prepare an mRNA molecule, thereby obtaining the mRNA vaccine for the echinococcosis. Finally, mRNA molecules are wrapped in lipid nanoparticles through a microfluidic method to form the mRNA vaccine for the echinococcosis, and immune effect evaluation is carried out on the mRNA vaccine for the echinococcosis. Experiments prove that the prepared mRNA vaccine for the echinococcosis can activate humoral immunity and cellular immunity of mice at the same time, can provide an effective protection effect for the mice attacking insects, and has a wide application prospect in the aspect of preventing and / or treating the echinococcosis.

The invention discloses a mycobacterium tuberculosis tandem DNA vaccine W543 as well as a preparation method and application thereof. The DNA vaccine W543 provided by the invention is a novel mycobacterium tuberculosis DNA vaccine with multiple antigen immunodominance epitopes, which is constructed by connecting polypeptides or epitope coding genes of a mycobacterium tuberculosis proliferation period antigen and a latent related antigen in series through a linker by virtue of genetic engineering and inserting the polypeptides or epitope coding genes into an eukaryotic expression vector pVAX1. Experiments prove that the mycobacterium tuberculosis specific tandem DNA vaccine W543 disclosed by the invention is used as an immunomodulatory preparation, mainly stimulates immune response of Th1 type, and can significantly enhance the specific cellular immune function of mice; as a preventive treatment preparation, the bacterial count of lung and liver tissues can be reduced, the lesion range of the lung tissues is remarkably reduced, the lesion is relieved, and the treatment effect is slightly superior to that of an existing commercial tuberculosis latent infection prevention and treatment preparation, namely, microkalidium vaccine.

The present invention provides a microfluidic detection chip for tuberculosis-specific cellular immunity, belonging to the technical field of Mycobacterium tuberculosis detection. The chip is primarily composed of a three-layer structure, assembled sequentially from bottom to top: a chip bottom sealing plate, a chip substrate, and a chip top sealing plate. The chip is equipped with detection units for multiple samples, capable of simultaneously performing IGRA detection of negative controls, positive controls, and a sample control of 1-8 test samples. Furthermore, the present invention provides an assembly process for a centrifugal microfluidic detection chip for tuberculosis-specific cellular immunity, as well as a detection method and application of chip-based IGRA using the chip. The chip-based IGRA demonstrated a 100% overall concordance rate between test results and those of conventional IGRA. Furthermore, the chip-based IGRA enables detection of very small numbers of test samples, while improving the throughput and speed of IGRA detection, thus showing significant application prospects for IGRA detection of large numbers of clinical samples.

The invention discloses copper selenide / tricalcium silicate bone cement. The bone cement comprises a liquid phase component and a solid phase component, the liquid phase component is water, and the solid phase component is tricalcium silicate powder and copper selenide nanoparticles. Compared with the existing tricalcium silicate bone cement, the tricalcium silicate bone cement has the advantages that by introducing a trace amount of copper selenide nanoparticles, not only can the hydration and coagulation time of tricalcium silicate be shortened, but also the porosity and degradation rate of the tricalcium silicate after coagulation and solidification can be reduced, the compressive strength can be improved, the stimulation effect on ALP activity of MC3T3-E1 cells can be enhanced, the survival rate of the MC3T3-E1 cells can be improved, and the application prospect is broad. The immunogenic apoptosis of K7M2-wt cells is promoted, and the tumor growth rate is reduced. Besides, the introduction of the copper selenide nanoparticles can also endow the tricalcium silicate bone cement with the performance of temperature rise under near-infrared light, so that in clinical application, the tricalcium silicate bone cement can be further combined with a near-infrared technology to realize ablation of bone tumors, and a new strategy is provided for treatment of the bone tumors.

The invention belongs to the technical field of biology, and discloses an mRNA vaccine, and the mRNA vaccine is an mRNA vaccine encapsulated by LNP. The mRNA is designed according to the gene sequence of the avian influenza H5N6 strain, the mRNA vaccine disclosed by the invention is an mRNA vaccine obtained through LNP encapsulation, the vaccine can reach the action point more accurately through encapsulation, meanwhile, the mRNA part of the vaccine is designed according to the gene sequence of the avian influenza H5N6 strain, and in addition, the mRNA part of the vaccine can reach the action point more accurately. A challenge test shows that the mRNA vaccine not only has good humoral immunocompetence, but also has good cellular immunocompetence.

The invention relates to an mRNA (messenger Ribonucleic Acid) vaccine targeting FomA and application of the mRNA vaccine in immunotherapy of esophageal squamous carcinoma in the technical field of tumor immunotherapy. The problems that in the prior art, a specific targeting vaccine for the fusobacterium nucleatum membrane protein FomA lacks, traditional antibiotics can only kill extracellular bacteria and cannot remove intracellular colonized fusobacterium nucleatum, and cellular immunity cannot be effectively activated to remove fusobacterium nucleatum colonized in tumor tissue; the immunotherapy drug resistance of esophageal squamous carcinoma caused by fusobacterium nucleatum infection is difficult to reverse. According to the technical scheme, an mRNA molecule with a fusobacterium nucleatum FomA extracellular domain tandem repeat sequence and a lipid nanoparticle delivery system are coded, an extramembrane segment tandem repeat immune enhancement technology is adopted for design, two extracellular ring sequences are repeated for 2-5 times and connected through a connector sequence, lipid nanoparticles are composed of optimized quaternary lipids, and the lipid nanoparticles are prepared from the quaternary lipids. And a PD-1 monoclonal antibody is combined to activate FomA specific CD8 + T cell immunoreaction, so that comprehensive removal of intracellular and extracellular bacteria and bacteria targeted immune remodeling are realized.

The invention belongs to the technical field of medicines, and discloses a mycobacterium tuberculosis fusion protein LT57 construction and expression purification method, a mycobacterium tuberculosis cell wall antigen Rv0518 and mycobacterium tuberculosis PE / PPE family antigens PE25 and PPE41 are fused, and the fusion protein PE25-linker-PPE41-Rv0518 is constructed by connecting the fusion protein Rv0518 and the fusion protein PPE41 through flexible peptide fragments. The fusion protein is expressed in a prokaryotic expression vector E.coli BL21 (DE3), and is obtained through column chromatography purification. The fusion protein LT57 and an adjuvant DP are combined to construct a tuberculosis subunit vaccine, a relatively strong specific cellular immune response aiming at a specific antigen of mycobacterium tuberculosis can be induced in a mouse body, the long-term generation of memory T cells is promoted, and the tuberculosis subunit vaccine has relatively strong immunogenicity. The novel fusion protein LT57 is successfully constructed, expressed and purified, and antigen-specific cellular immunity and humoral immunity can be induced.

The invention belongs to the field of biological medicine and materials, and particularly relates to a nano vaccine for promoting antigen cross presentation and a preparation method and application thereof, the method comprises the following steps: inducing tumor cell immunogenicity death to obtain a tumor cell immunogenicity death product; a polylactic acid-glycolic acid copolymer is mixed with alpha-galactosylceramide to serve as a carrier, a tumor cell immunogenicity death product, racimod and endosome-lysosome escape promoting peptide are wrapped, and the nano vaccine is prepared. The method for inducing immunogenic death of the tumor cells comprises the following steps: co-incubating the tumor cells and the iridium composite oligoarginine polypeptide and / or irradiating the tumor cells with the photosensitizer by laser. The nano vaccine has efficient antigen cross presentation capability, and can stimulate expression of dendritic cell co-stimulation signals and secretion of cell factors in multiple ways, so that the biological effect of synergistically activating cellular immunity is achieved.

The invention discloses a ganoderma lucidum peptide for enhancing immunity as well as a preparation method and application thereof, and belongs to the technical field of functional peptide preparation. The ganoderma lucidum peptide provided by the invention contains various active ingredients / nutritional ingredients, is high in utilization rate of ganoderma lucidum, can improve the health level of intestinal tracts, promotes absorption and utilization of nutrient substances by the intestinal tracts, and provides a fundamental material guarantee for improving the immunity of the organism; immune cells are activated, and related lymphatic tissues of intestinal tracts are stimulated, so that the effects of regulating cellular immunity and humoral immunity levels are achieved; the preparation method provided by the invention does not use high-temperature, high-pressure and toxic and harmful reagents, has mild conditions, and is simple, easy to operate and environment-friendly; no toxic and harmful substances are generated, and generated filter residues can be directly used as animal feed or plant fertilizer; the prepared ganoderma lucidum peptide is small in molecule, high in activity, rich in active substance variety, high in yield and easy to absorb and utilize by organisms.

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 belongs to the technical field of autoimmune skin disease immunotherapy, and provides a three-target novel chimeric autoantibody receptor structure which comprises three chimeric receptors through two connecting peptides, specifically, a first chimeric autoantibody receptor comprises a Dsg1 extracellular structural domain; the second chimeric autoantibody receptor comprises a Dsg3 extracellular structural domain; the third chimeric antigen receptor comprises an extracellular domain capable of targeting a B cell associated antigen; wherein the Dsg1 extracellular structural domain is an extracellular structural domain of desmosome core glycoprotein 1; the Dsg3 extracellular structural domain is the extracellular structural domain of desmosome core glycoprotein 3. In-vitro experiments and animal experiments verify that the novel three-target CAAR-T cells can significantly increase the release of cytokines, enhance the targeted killing activity of the cytokines, and show better multiplication capacity; a novel cellular immunotherapy technology is provided for treating autoimmune skin diseases, and the application of CAAR-T in the field of autoimmune disease treatment can be expanded.

The invention belongs to the technical field of cellular immunotherapy, and particularly relates to a targeted MSLN chimeric antigen receptor macrophage, a preparation method thereof and application of the targeted MSLN chimeric antigen receptor macrophage to treatment of MSLN positive tumors. According to the present invention, the chimeric antigen receptor modified engineering immune cell specifically targeting MSLN is prepared by using the chimeric antigen receptor modified macrophage technology, the preparation method has simple steps, and the obtained novel engineering immune cell can specifically recognize tumor cells, can more effectively target and attack the tumor cells, has a high tumor killing rate, and can be used for preparing the MSLN-targeted engineering immune cell. The compound can be used for preparing anti-tumor products, especially for preparing drugs for treating MSLN positive tumors, especially for preparing drugs for treating ovarian cancer malignant pleural mesothelioma, pancreatic cancer and part of lung cancer, and has good industrial application prospects.

The invention discloses mucosal immune-enhanced recombinant lactobacillus for expressing PEDV (porcine epidemic diarrhea virus) S1 protein as well as a construction method and application of the mucosal immune-enhanced recombinant lactobacillus. The mucosal immune-enhanced recombinant lactobacillus contains a recombinant lactobacillus expression vector for expressing PEDV S1 protein, the amino acid of the PEDV S1 protein is fused with M cell targeting peptide (Co1) and dendritic cell targeting peptide (6aa), the carboxyl terminal of the PEDV S1 protein is fused with a mucosal immune adjuvant (LTB), and the connection sequence of all the parts is Co1-6aa-S1-LTB. According to the mucosal immune enhanced recombinant lactobacillus constructed by the invention, through the synergistic effect of the targeting peptide (DC / MC targeting peptide) and the adjuvant (LTB), the mucosal immune response efficiency (including intestinal mucus SIgA and serum IgG levels) of a PEDV S1 antigen is remarkably improved, humoral immunity, cellular immunity and mucosal immune responses of pregnant animals can be remarkably induced, maternal antibodies are generated, and the immune response efficiency of the pregnant animals is remarkably improved. The intestinal SIgA level of newborn animals is improved, and an effective technical means is provided for prevention and treatment of PED.

The invention discloses a double-epitope CAR targeting CLL1, a double-epitope CAR-T cell and application of the double-epitope CAR and the double-epitope CAR-T cell, and belongs to the technical field of cellular immunotherapy. The technical problem to be solved by the invention is how to improve the killing activity of the CLL1-targeted chimeric antigen recipient cell on CLL1-positive tumor cells and / or the immunosuppression effect of resisting a tumor microenvironment. The invention specifically discloses a chimeric antigen receptor with an amino acid sequence as shown in SEQ ID No.1, a fusion protein with an amino acid sequence as shown in SEQ ID No.3, and a double-epitope CAR-T cell constructed by using the chimeric antigen receptor and the fusion protein. The double-epitope CAR-T cell disclosed by the invention can well secrete T cell specific effector molecules IFN-gamma, effectively and specifically kill CLL1 + target cells, and has good in-vivo tumor killing activity. The antibody can be used for immunotherapy of CLL1 target related diseases, and has a wide clinical application prospect.

The invention belongs to the technical field of medicines, and discloses application of an adeno-associated virus vector in preparation of medicines for preventing and treating RSV infection and / or diseases caused by RSV. According to the invention, a recombinant adeno-associated virus vector is adopted for the first time to construct a medicine for preventing and treating RSV infection or diseases caused by RSV infection, and based on this, the invention provides a nucleic acid molecule which comprises: (a1) a first region which comprises a first adeno-associated virus inverted terminal repeat sequence, and (a2) a second region which comprises a second adeno-associated virus inverted terminal repeat sequence; and (a2) a second region comprising a gene encoding a respiratory syncytial virus antigen; the recombinant adeno-associated virus containing the nucleic acid molecule can generate better humoral immune effect and cellular immune effect, has a certain serum neutralization effect on strains of A and B subtypes of RSV, and particularly, when the antigen is a fusion protein of the respiratory syncytial virus or a fusion protein mutant of the respiratory syncytial virus, the recombinant adeno-associated virus has a certain serum neutralization effect on the strains of A and B subtypes of the RSV. The recombinant adenovirus vector containing the nucleic acid molecule can successfully realize the expression of the F protein before RSV fusion.

In order to seek an echinococcosis antigen which has good immunogenicity and can activate an organism to generate an effective immune response against echinococcosis granulosa infection, the invention provides an echinococcosis multi-epitope antigen and application thereof in preparation of a vaccine for preventing echinococcosis. The multi-epitope antigen is formed by sequentially connecting CTLA-4-lgV, a T cell epitope of EgA31, a T cell epitope of EgG1Y162, a B cell epitope of EgA31 and a B cell epitope of EgG1Y162 in series, the multi-epitope antigen can be specifically combined with serum of a cystic echinococcosis patient, a mouse immunized by a vaccine can generate specific B cell response and generate specific cellular immunity and an antibody, and the multi-epitope antigen has good immunogenicity.

The application provides a cell fixing solution for a myasthenia gravis antibody spectrum (IgG) detection kit (cellular immunofluorescence method) and a product and application thereof, and relates to the technical field of in-vitro detection. The cell fixing solution provided by the application is composed of polyoxymethylene, formaldehyde, acetic acid, raffinose and a buffer solution, can effectively fix the cell morphology, maximally retains the natural spatial conformation and antigen epitope integrity of myasthenia gravis related antigens AChR, Titin, RyR1, MuSK and LRP4, reduces the problems of antigen denaturation, epitope shielding and protein loss in the fixing process, can efficiently and accurately realize the synchronous joint detection of various specific antibodies, and the myasthenia gravis antibody spectrum (IgG) detection kit (cellular immunofluorescence method) prepared by the application has stable detection results, and has important clinical application value and industrial popularization prospect.

The present invention relates to the field of medical testing. Specifically, the present invention provides a diagnostic model for predicting the prognosis of CAR-T cell immunotherapy for gastric cancer and its application. For the first time, the present invention systematically analyzed the content and spatial distribution map of the microenvironment components of CLDN18.2-positive gastric cancer tissue samples by integrating multiple fluorescent immunohistochemistry detection and whole-slice digital imaging quantitative analysis methods. Through multidimensional evaluation of the tumor microenvironment under the treatment background of CT041, a diagnostic model for predicting the prognosis of CAR-T cell immunotherapy for gastric cancer was established for the first time, which enables accurate screening of beneficiary populations and risk stratification before treatment, guides treatment selection, and improves treatment efficacy.

The invention belongs to the technical field of biological medicine, and particularly relates to a culture method and application of a hematological malignant tumor organoid. The culture method comprises the following steps: S01, obtaining a tumor cell sample; s02, preparing a bone marrow microenvironment simulation matrix, and resuspending tumor cells; s03, a specific culture medium is added for hematoma organoid culture; s04, performing phenotype identification on the cultured hematological malignant tumor organoid; and hematological malignant tumor organs with phenotypes close to those of bone marrow cells of the patient are screened out. According to the method system disclosed by the invention, the hematoma organoid is successfully cultured and is further subjected to phenotype identification, and the screened hematoma organoid is close to the cellular immune phenotype of a patient and can be used for accurate detection of clinical patient drug sensitivity and effective test of potential effective target drugs.

This invention relates to the field of biopharmaceutical technology, disclosing a QS-21 saponin adjuvant, its preparation method, and its applications. The adjuvant is a composite liposome comprising a liposome backbone composed of distearate phosphatidylcholine and cholesterol, with QS-21 saponin, monophosphatidyllipid A, and a local anesthetic co-encapsulated therein. This invention solves the common problem of high reactivity and immunogenicity in potent adjuvants by co-encapsulating immunostimulatory and analgesic components on the same nanocarrier, achieving synergistic delivery at the injection site, thereby precisely inhibiting adjuvant-induced pain and swelling. This co-encapsulation structure avoids the potential inhibitory effect of free anesthetics on the immune system, fully preserving the adjuvant's potent humoral and cellular immune-enhancing activity. This invention provides a new technical solution for developing vaccines with both high safety and strong immunogenicity.

Described herein are covalently modified polypeptide antigens with improved immunogenicity and / or stability, as well as compositions, cells, and methods related to the polypeptide antigens. The polypeptide antigens are covalently conjugated to one or more steroid acid moieties to improve their stability and / or to elicit improved cellular immunity or improved cellular and humoral immunity against the antigens after administration to a subject. The steroid acids include bile acids and bile acid analogs that enhance endosomal trapping of cargo by enhancing the enzymatic cleavage of endosomal membrane- ensheathed sphingomyelin to ceramide and / or endosomal escape. The steroid acid moieties can be preconjugated to a peptide, and the steroid acid-peptide moiety is subsequently conjugated to the polypeptide antigen. The peptide can comprise one or more domains that confer additional functionality to the modified polypeptide antigen.