40 results about "Autologous tumor" patented technology

The invention belongs to preparation of biological cell formulations, and in particular relates to a preparation method of dendritic cell (DC) vaccine loaded with autologous tumor associated holoantigen. The preparation method comprises the following steps: preparing the autologous tumor associated holoantigen, collecting and separately culturing DCs, impacting the DCs by the autologous tumor associated holoantigen, maturing the DCs and preparing autologous tumor antigen specific DC vaccine. The invention solves the problems in the prior art that the immunogenicity of tumor antigen is not strong enough, the antigen target spots are incomplete, the tumor antigens of most tumor patients are difficult to acquire, and the like. The DC vaccine provided by the invention has the advantages of effectively inducing tumor antigen specific cytotoxic T lymphocyte (CTL) in vitro and in vivo, efficiently generating specific cytotoxicity on tumors, having high overall effective rate and no obvious toxic side effects in clinical application, and the like.

The present invention discloses that an intratumoral injection of: i) glycolipids with α-gal epitope; ii) gene vectors comprising an α1,3galactosyltransferase gene; or iii) a mixture of α1,3galactosyltransferase, neuraminidase, and uridine diphosphate galactose results in tumor regression and / or destruction. Binding of the natural anti-Gal antibody to de novo expressed tumoral α-gal epitopes induces inflammation resulting in an anti-Gal antibody mediated opsonization of tumor cells and their uptake by antigen presenting cells. These antigen presenting cells migrate to draining lymph nodes and activate tumor specific T cells thereby converting the treated tumor lesions into in situ autologous tumor vaccines. This therapy can be applied to patients with multiple lesions and in neo-adjuvant therapy to patients before tumor resection. In addition to the regression and / or destruction of the treated tumor, such a vaccine will help in the immune mediated destruction of micrometastases that are not detectable during the removal of the treated tumor.

The present invention discloses that an intratumoral injection of: i) glycolipids with α-gal epitope; ii) gene vectors comprising an α1,3galactosyltransferase gene; or iii) a mixture of α1,3galactosyltransferase, neuraminidase, and uridine diphosphate galactose results in tumor regression and / or destruction. Binding of the natural anti-Gal antibody to de novo expressed tumoral α-gal epitopes induces inflammation resulting in an anti-Gal antibody mediated opsonization of tumor cells and their uptake by antigen presenting cells. These antigen presenting cells migrate to draining lymph nodes and activate tumor specific T cells thereby converting the treated tumor lesions into in situ autologous tumor vaccines. This therapy can be applied to patients with multiple lesions and in neo-adjuvant therapy to patients before tumor resection. In addition to the regression and / or destruction of the treated tumor, such a vaccine will help in the immune mediated destruction of micrometastases that are not detectable during the removal of the treated tumor.

The invention discloses a method for preparing a tumor-specific DC vaccine by applying CD34+ cells in umbilical cord blood. The method comprises (1) a step of preparing autologous tumor-related holoantigen; (2) a step of obtaining the umbilical cord blood; (3) a step of obtaining mononuclear cells derived from the umbilical cord blood; (4) a step of purifying CD34+ cells in the mononuclear cells derived from the umbilical cord blood; (5) performing induction culture for a precursor DC; (6) a step of performing amplification and culture of an immature DC; and (7) a step of preparing the DC vaccine.

A method of preparing autologus T-lymphocytes for re-introduction into a patient having cancer, which method comprises obtaining peripheral blood mononuclear cells (PBMCs) from a patient immunized with an antigen of the cancer, stimulating the PBMCs with the antigen of the cancer in vitro, transducing the PBMCs with a retrovial vector, which (a) comprises and expresses a human interleukin-2 (IL-2) coding sequence operably linked to a retroviral promoter, (b) does not comprise an exogenously introduced gene that enables phenotypic selection, and (c) comprises a viral envelope that efficiently transduces CD8+ T-lymphocytes; a method of preparing autologous tumor-infiltrating lymphocytes (TILs) for reintroduction into a patient having cancer, which method comprises obtaining TILs from a tumor of the patient, optionally immunized with an antigen of the cancer, optionally stimulating the TILs with the antigen of the cancer in vitro, and transducing the TILs with the aforementioned retroviral vector, compositions comprising cells obtained in accordance with such methods; and methods of treating a patient having cancer by administering to the patient cells obtained in accordance with such methods or compositions comprising same.

The invention provides an autologous dendritic cell activated tumor-infiltrating T-lymphocyte preparation method. The method has the following characteristics that: a tumor-infiltrating T-lymphocyte from a cancer patient is activated and amplified in a large quantity by using a dendritic cell loaded by an autologous tumor antigen as a trophoblast cell and interleukin-2, and has a highly active anti-tumor cell toxic response. The invention further provides an autologous tumor-infiltrating T-lymphocyte kit prepared according to the method, and the kit has an efficient anti-tumor function.

The invention relates to a preparation method and application of an autologous tumor vaccine. The method comprises the following specific steps: radiating and / or heating autologous tumor cells to greatly excite the antigenicity of the autologous tumor cells and enhance the presentation property of the antigen by using heat shock proteins; and inactivating the tumor cells and adding an adjuvant toobtain the vaccine. The vaccine prepared by using the method has the special advantages of high presentation property and high tumor immunogenicity, and can be used for greatly exciting the body fluidand cellular immune response of tumor patients to autologous tumors, monitoring immune response, and timely adjusting a usage method of the novel vaccine and adjuvant treatment, so that the aims of improving the antigenicity and metastatic tumor effect and prolonging the survival time of tumor patients are fulfilled.

A method is described for the identification of specific tumor antigens by means of the selection of cDNA display libraries by using sera, characterised in that said selection is accomplished with the phage display technique, and in particular said selection is accomplished by means of the SEREX technique (serological analysis of autologous tumor antigens through the expression of recombinant cDNA). The method according to the invention described herein advantageously combines the SEREX approach with the potency of the phage display technique defined above, at the same time avoiding the drawbacks characteristic of the SEREX technique. The so identified antigens are useful for the preparation of medicaments for the treatment of tumors.

The present invention concerns methods and compositions for administering a binding agent to a patient wherein the patient generates a response to autologous tumor. The binding agents target apoptotic tumor cells and facilitates the uptake of these apoptotic tumor cell are taken up by dendritic cells or other antigen presenting cells for processing and presentation to the immune system without the expression of circulating tumor-associated antigen (or without the need of circulating tumor antigen).

Autologous anti-cancer vaccines and methods of manufacture and treatment are provided, including expansion of individual patient-derived tumor cells in an immune-compromised animal(s) to attain, quantitatively and qualitatively, sufficient material for efficacious vaccine production and utilization, to elicit an immune response against micrometastases and / or recurrence in the individual patient following tumor excision.

The invention relates to the treatment of cancer, and particularly to the treatment of cancers of the central nervous system, such as glioblastoma multiforme. A dual therapeutic approach is provided, including the administration of a dendritic cell-based cancer vaccine and a regimen of chemotherapy. The two therapies may be administered concurrently with one another and / or with an initial vaccination preceding chemotherapy. In various embodiments, the dendritic cell-based cancer vaccine includes either primed or unprimed dendritic cells; for instance, the dendritic cells may be autologous tumor antigen-presented dendritic cells. The dual therapeutic approach of the instant invention beneficially influences the chemosensitivity of a mammal with cancer.

The invention relates to the technical field of cell culture, in particular to a tumor neoantigen specific tumor infiltration lymphocyte co-culture method which is characterized by comprising the following steps: S1, tumor neoantigen preparation: respectively collecting the tissues of lung cancer (N1), pancreatic cancer (N2), bile duct cancer (N3), triple-negative breast cancer (N4) and melanoma tumor (N5), separating tumor cells, andcollecting normal tissues of corresponding individuals; comparing the all-exon sequencing and normal tissue and tumor tissue sequencing results to determine all amino acid mutations, then designing a gene construct containing all mutant peptide sequences and synthesizing a long-chain polypeptide according to a neoantigen coded by a mutant gene. The TIL cells harvested by designing a co-culture method of tumor neoantigen specific tumor infiltration lymphocytes can effectively kill autologous tumor target cells, can induce immune cells to have multiple target spots, are free of limitation of cancer species, and have an immune memory effect.

The invention discloses a method for preparing a tumor-specific DC vaccine by applying mononuclear cells of umbilical cord blood. The method comprises (1) a step of preparing autologous tumor-related holoantigen; (2) a step of obtaining the umbilical cord blood; (3) a step of obtaining the mononuclear cells derived from the umbilical cord blood; (4) a step of performing induction culture for a precursor DC of the mononuclear cells derived from the umbilical cord blood; (5) a step of performing amplification and culture of an immature DC; and (6) a step of preparing the DC vaccine.

A method is disclosed for treating a cancer in a subject. The method comprises administering to the subject a composition comprising a therapeutically effective amount of a checkpoint inhibitor and a therapeutically effective amount of a tumor vaccine. In some embodiments, the tumor vaccine comprises radiated autologous tumor cells and a cell line engineered to express granulocyte- macrophage colony-stimulating factor (GM-CSF) and cluster of differentiation 40 (CD40) ligand. In some embodiments, the checkpoint inhibitor comprises an anti-programmed death-1 (anti-PD-1) antibody (e.g., BMS 936558), anti-programmed death ligand-1 (anti-PD-L1) antibody (e.g., cloneMIHI), anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4) antibody (e.g., Ipilimumab, BMS), or any combination thereof.

The invention belongs to preparation of biological cell formulations, and in particular relates to a preparation method of dendritic cell (DC) vaccine loaded with autologous tumor associated holoantigen. The preparation method comprises the following steps: preparing the autologous tumor associated holoantigen, collecting and separately culturing DCs, impacting the DCs by the autologous tumor associated holoantigen, maturing the DCs and preparing autologous tumor antigen specific DC vaccine. The invention solves the problems in the prior art that the immunogenicity of tumor antigen is not strong enough, the antigen target spots are incomplete, the tumor antigens of most tumor patients are difficult to acquire, and the like. The DC vaccine provided by the invention has the advantages of effectively inducing tumor antigen specific cytotoxic T lymphocyte (CTL) in vitro and in vivo, efficiently generating specific cytotoxicity on tumors, having high overall effective rate and no obvious toxic side effects in clinical application, and the like.

The invention relates to pharmaceutical compositions comprising α-Gal BOEL for use in treating patients with tumors. The invention also relates to methods of treating tumors using said compositions. The invention discloses that following intratumoral injection of α-Gal BOEL, binding of the natural anti-Gal antibody to de novo expressed tumoral α-Gal epitopes induces inflammation resulting in an anti-Gal antibody mediated opsonization of tumor cells and their uptake by antigen presenting cells. These antigen presenting cells migrate to draining lymph nodes and activate tumor specific T cells thereby converting the treated tumor lesions into in situ autologous tumor vaccines. This therapy can be applied to patients with multiple lesions and in neo-adjuvant therapy to patients before tumor resection. In addition to the regression and / or destruction of the treated tumor, such a vaccine will help in the immune mediated destruction of micrometastases that are not detectable during the removal of the treated tumor. The invention further teaches the enhancement of anti-tumor α-Gal BOEL treatment by the use of antibodies that inhibit the activity of immunological checkpoints molecules.

The invention discloses a method for preparing a tumor-specific DC vaccine by applying CD34+ cells in umbilical cord blood. The method comprises (1) a step of preparing autologous tumor-related holoantigen; (2) a step of obtaining the umbilical cord blood; (3) a step of obtaining mononuclear cells derived from the umbilical cord blood; (4) a step of purifying CD34+ cells in the mononuclear cells derived from the umbilical cord blood; (5) performing induction culture for a precursor DC; (6) a step of performing amplification and culture of an immature DC; and (7) a step of preparing the DC vaccine.

The invention relates to a method for screening tumor-specific TCR, which belongs to the technical field of tumor immunity. In the present invention, after co-incubating tumor cells of tumor patients and tumor infiltrating T cells (TILs) corresponding to autologous tumor cells in vitro, these cells are subjected to single-cell transcriptome and TCR group sequencing to obtain the TCR sequence of each TILs cell, for For all TILs cells expressing the same TCR, the average value of the expression values ​​of the 10 T cell markers was used as the activation score of the TCR marker. According to the activation score, the one with the higher score was selected as the TCR corresponding to the tumor-specific T cell.

Provided herein are vaccine compositions containing at least one retrievable biocompatible macrocapsule containing immuno-isolated allogeneic cells that secrete an immunomodulator such as GM-CSF (granulocyte-macrophage colony stimulating factor) and an antigenic component such as autologous tumor cells or infectious agents. Also provided are kits and pharmaceutical compositions containing the vaccine compositions as well as methods of use thereof for therapeutic or preventative vaccination against tumors or infectious agents.