30 results about "Antitumor response" patented technology

To provide a novel therapeutic strategy for treating cancers expressing embryonic antigens.SOLUTION: The inventors have developed a metastatic 4T1 breast tumor model in BALB / c mice. The inventors have showed that vaccination with xenogeneic embryonic stem cells in combination with valproic acid (VPA) generates a higher antitumor response against a breast cancer and inhibits metastasis development. The inventors have demonstrated that these responses are only achieved by the addition of valproic acid in a therapeutic regimen compared to the use of ESC or iPSC alone. Thus, the inventors provide a novel therapeutic strategy for treating cancers expressing embryonic antigens. The present invention therefore relates to a method for treating a subject suffering from cancer, comprising the steps of administering to the subject simultaneously, separately or sequentially a therapeutic amount of i) a population of pluripotent cells and ii) a compound selected from the group that activates MHC expression as a combined preparation.SELECTED DRAWING: None

The present invention relates to citrullinated Cytokeratin peptides that can be used in cancer immunotherapy. The modified peptides may be used as vaccines or as targets for T cell receptor (TCR) and adoptive T cell transfer therapies. Such vaccines or targets may be used in the treatment of cancer.

The application discloses application of ginsenoside Rf in preparation of an enhancer of a PD-1 inhibitor antitumor drug, and the ginsenoside Rf has the effects of improving a PD-1 inhibitor antitumor response rate, prolonging a survival period, and reducing toxicity, and has a significant advantage in enhancing PD-1 inhibitor treatment of tumors.

The invention discloses oral multi-drug delivery hydrogel as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. According to the delivery hydrogel, spirulina platensis and traditional Chinese medicine ingredient astragalus polysaccharide are used as raw materials and are added into network-shaped hydrogel formed by combining carboxymethyl chitosan / sodium alginate. The method is easy to implement, safe in component and high in encapsulation efficiency. The composite hydrogel is stated to have the following effects: after oral administration, the medicine can be protected to completely pass through the stomach, the intestinal retention is prolonged, and the medicine can be continuously released at the focus part; the immune checkpoint inhibitor related intestinal inflammation is relieved, and the anti-tumor effect of the immune checkpoint inhibitor is assisted; and noninvasive monitoring of the medicine in the body is realized. According to the invention, a bioactive material is used as a potential treatment strategy for enhancing anti-tumor reaction and relieving immune checkpoint inhibitor-related adverse reaction, and can be more widely applied to treatment of pathological changes related to intestinal microbiome imbalance.

To provide methods for treating cancer.SOLUTION: Provided are methods comprising the administration of donor-derived allogeneic γδ-T cells (gamma / delta-T cells) to a subject. In such methods, at least one lymphodepletion treatment or a Hematopoietic Stem Cell (HSC) transplant is administered to the subject, followed by the subsequent administration of donor-derived allogeneic γδ-T cells. The methods also comprise expanding the donor-derived allogeneic γδ-T cells ex vivo prior to administration to the subject. Such methods comprise exposing donor-derived allogeneic γδ-T cells to one or more γδ-T cell expansion compounds. Such a therapy induces an antitumor response in the subject.SELECTED DRAWING: None

This invention discloses a STAT3-mutated cell product and its uses, belonging to the interdisciplinary field of genetic engineering and tumor immunotherapy. Through saturation mutation screening, this invention is the first to discover that STAT3 gain-of-function mutations promote CAR-T anti-tumor responses. Furthermore, through cell and animal experiments, it is demonstrated that activating STAT3 can alleviate CAR-T cell immune exhaustion and significantly enhance the in vivo and in vitro killing ability of CAR-T cells against tumor cells, thereby improving the efficacy of anti-tumor therapy. This invention provides a new therapeutic target and strategy for the field of tumor immunotherapy, possessing significant scientific and clinical application value.

The invention relates to siRNA as well as a conjugate and application thereof, and belongs to the technical field of molecular biology and biological medicine. The siRNA comprises a positive-sense strand and an antisense strand. The conjugate comprises an aptamer and siRNA (small interfering Ribonucleic Acid). The siRNA and the conjugate provided by the invention are good in targeting property and high in safety, enter cancer cells (such as liver cancer cells) without the help of an exogenous transfection agent, and realize efficient knock-down of an immune checkpoint Nectin-2, so that the anti-tumor reaction of T cells is activated, and the siRNA and the conjugate are used for precise immunotherapy of tumors (such as liver cancer). The conjugate provided by the invention can be autonomously delivered to tumor cells without a transfection agent, quickly enters cytoplasm of the tumor cells without the help of lipidosome, polymer or viral vector, and generates a functional effect. The delivery strategy is high in safety, has unique practical value, and is different from a current mainstream delivery system in the RNA interference field.

Disclosed herein is a method for enhancing antitumor T cell responses in subjects. The method involves administering to the subject in need thereof a composition comprising a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. This method is particularly useful in subjects with deficient STING expression in the tumor cells. Therefore, also disclosed is a method for treating a tumor in a subject that involves detecting in a biopsy sample from the subject reduced STING expression, reduced cGAS expression, or a combination thereof; and then administering to the subject a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. The method can further involve administering to the subject a therapeutically effective amount of a STING agonist. The method can further involve administering to the subject tumor infiltrating lymphocytes (TILs), such as HLA-matched TILs.

The invention features methods and compositions for eliciting an anti-tumor response in a subject comprising administering to the subject a pHLIP● construct comprising an antibody recruiting molecule linked to one or more pHLIP● peptides by a non-cleavable linker compound. The construct increases the amount of the antibody recruiting molecule on the surface of a diseased cell.

The invention belongs to the technical field of biology, and particularly discloses application of a CAR-NK cell combined with a T cell in treatment of lymphoma and a method for improving survival of NK cells in an anti-tumor model. On one hand, the invention provides application of two rounds of medication of CAR-NK cells and T cells in treatment of lymphoma, and the CAR-NK cells are obtained by transfecting NK cells with CD19CAR autosecreting IL-15 and CCL21; on the other hand, the invention provides a method for improving the survival of the NK cells in an anti-tumor reaction model or an anti-tumor reaction biological model. The method comprises the step of modifying the NK cells to enable the NK cells to secrete IL-15 and CCL21 at the same time. In the disclosure, it is clear that the CAR-NK cell combined T cell co-secreting IL-15 and CCL21 can more effectively play a therapeutic effect on lymphoma, and particularly, when the CAR-NK cell combined T cell co-secreting IL-15 and CCL21 adopts two rounds of drug administration, the therapeutic effect is remarkably improved compared with that of single rounds of drug administration. Meanwhile, a new method is provided for improving the survival of the NK cells in various anti-tumor models.

Vectors or nucleic acid compositions encoding polypeptides of albumin fused to Flt3L, induce circulating dendritic cells and generate an anti-tumor response. In preferred aspects, the compositions are delivered via electroporation and possess more persistent bioactivity in targeted organs.

Provided herein are methods of modulating an immune response to a tumor or cancer cell in a patient, treating cancer or a tumor in a cancer patient, eliciting an anti-cancer or tumor response in a patient, or treating or ameliorating an infection in a subject in need thereof. The methods comprise modulating expression or activity of G Protein-Coupled Receptor 25 (GPR25) in a T cell in the patient.

A non-viral vector comprising, from 5' to 3', a first coding region flanked by two transposon terminal inverted repeat sequences, an inducible promoter, a specific combination of genes whose expression is localized to the tumor microenvironment and whose function is to mediate CAR persistence and anti-tumor mechanisms to stimulate or enhance the patient's anti-tumor response; a second promoter and coding region expressing one or more artificial immune surveillance chimeric antigen receptors (AI-CAR), and a truncated CD20 or truncated EGFR safety target. The polycistronic mRNA consists of a specific combination of transiently expressed anti-tumor mechanisms designed to stimulate the patient's anti-tumor response, the same as the AI-CAR vector.

The present invention provides compositions of dendritic cells contacted with extracellular vesicles and methods of use thereof. The extracellular vesicles lack or contain a reduce amount of microRNA-424. The dendritic cells may be administered to a subject diagnosed with cancer to treat the cancer or stimulate an anti-tumor response in the subject.

Disclosed herein is a method for enhancing antitumor T cell responses in subjects. The method involves administering to the subject in need thereof a composition comprising a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. This method is particularly useful in subjects with deficient STING expression in the tumor cells. Therefore, also disclosed is a method for treating a tumor in a subject that involves detecting in a biopsy sample from the subject reduced STING expression, reduced cGAS expression, or a combination thereof; and then administering to the subject a demethylating agent in an amount effective to demethylate STING proteins in the tumor cells. The method can further involve administering to the subject a therapeutically effective amount of a STING agonist. The method can further involve administering to the subject tumor infiltrating lymphocytes (TILs), such as HLA-matched TILs.

Disclosed herein are immune effector cells for use in adoptive cell transfer that have chemically- or genetically-inhibited PDHB (Pyruvate dehydrogenase E1 subunit beta) expression or activity. Also disclosed are methods of inhibiting or ablating PDHB expression in immune effector cells ex vivo and methods of using these cells to treat subjects with cancer. In some embodiments, the immune effector cells are further treated with a TIMS inhibitor or genetically engineered to ablate TIM3 expression. In some embodiments, the immune effector cells are further treated with a LAGS inhibitor or genetically engineered to ablate LAG3 expression. In some cases, the PDHB gene is disrupted by insertion of the gene encoding the chimeric receptor into the PDHB gene loci of the cell. Therefore, disclosed herein is a chimeric cell expressing a chimeric receptor.

In a strategy that allows cancer cells to escape from the immune system, the presence of transforming growth factor beta (TGF-beta) in the tumor microenvironment (TME) is one of the most effective immunosuppressive mechanisms for many types of tumors. Thus, depletion of TGF-beta is considered to be a promising effective therapeutic approach against cancer regardless of the type of tumor. However, the major obstacle to achieve this is that TGF-beta belongs to a small number of cytokines that must be activated once secreted. In addition, system targeting TGF-beta is associated with severe side effects because TGF-beta can maintain homeostasis of many tissues. Therefore, selective targeting TGF-beta activation in TME appears to be a reasonable method for enhancing anti-tumor response and avoiding side effects. Integrin [alpha] v [beta] 8 expressed on Treg specifically promotes TGF-[beta] activation and attenuates anti-CD8T cell response in different cancer TME in mice and humans. The inventors have generated neutralizing monoclonal antibodies against the beta 8 chain (Itg beta 8) of alpha v beta 8 integrin that specifically bind to Treg and selectively neutralize the ability of Treg to activate TGF-beta. Thus, the present invention relates to isolated anti-Itg [beta] 8 neutralizing antibodies that specifically bind to the [beta] 8 chain (Itg [beta] 8) of the [alpha] v [beta] 8 integrin expressed on Treg, and their use for the treatment of cancer.

Among the strategies allowing cancer cells to escape the immune system, the presence of Transforming growth factor beta (TGF-β) in the tumor micro-environment (TME) is one of the most potent immunosuppressive mechanisms for many types of tumors. Thus, depleting TGF-β is regarded as a promising potent therapeutic approach to fight cancers, regardless of the type of tumor. However, the major impediment for achieving this objective is that TGF-β belongs to the few cytokines that must be activated once secreted. Moreover, a systemic targeting of TGF-β is associated with profound side effects due to TGF-β ability to sustain the homeostasis of numerous tissues. Hence, selectively targeting of TGF-β activation within the TME appears as a rational approach to boost the anti-tumor response and avoid side effects. The integrin αvβ8 expressed on Tregs specifically promotes TGF-β activation and impairs the anti-CD8 T cell response within the TME of different cancers in both mice and humans. The inventors generated anti-β8 chain of αvβ8 integrin (Itgβ8) neutralizing monoclonal antibodies which specifically bind to Tregs and selectively neutralize the ability of Tregs to activate the TGF-β. Thus, the present invention relates to isolated anti-Itgβ8 neutralizing antibodies which specifically binds to β8 chain of αvβ8 integrin (Itgβ8) expressed on Tregs, and their uses for treating cancer.

The present disclosure provides a drug delivery system comprising trimetallic nanoparticles coated with biocompatible and water-soluble coating polymers, encapsulating the anticancer agent proscillaridin, for enhancing targeted tumor cell delivery while minimizing damage to healthy cells. More particularly to a drug delivery system containing tri-metallic nanoparticles composite loaded with an anticancer agent with polymeric coating with a potential to improve the antitumor reactivity and selectivity toward specific type of tumor cell lines.

Provided herein are methods for increasing the therapeutic efficiency of oncolytic bacterial therapeutics. Bacterial oncolytic therapies, especially the ones targeting tumor hypoxia such as C. novyi-NT, often encounter incomplete tumor clearance in less hypoxic tumoral areas and severe inflammatory reactions. In this study, we explored immune-modulating preconditioning to suppress the host neutrophils and significantly enhanced the antitumor efficacy of C. novyi-NT in animal models, including an orthotopic brain tumor model in rabbits. The optimized preconditioning agent, hydroxyurea, is clinically approved and C. novyi-NT has demonstrated manageable safety and promising antitumor responses in clinical trials. Thus, the proposed preconditioning of neutrophil suppression is readily translatable to patients undergoing C. novyi-NT trials or other oncolytic biologic therapies and could improve outcome.

The invention belongs to the field of biological medicine, and particularly relates to a composition for enhancing the non-small cell lung cancer treatment effect of NK cells and application of the composition. According to the present invention, the oncolytic adenovirus Ad-anti-TGF-beta RII, which is subjected to genetic engineering modification and encodes the TGF-beta inhibitor, is combined with the PD-1 antibody so as to achieve the efficient NK cell anti-tumor reaction, and improve the treatment effect of ICIs in NSCLC patients. The triple therapy developed by the invention can benefit advanced NSCLC patients who have drug resistance to immune checkpoint inhibitors (ICIs). Meanwhile, according to the triple therapy, after treatment, histopathologic analysis is carried out on heart, liver, lung and kidney tissues, all examined organs do not have pathological visible injuries, and it is indicated that the treatment has good safety. In a word, the triple therapy provided by the invention provides a new strategy for combined immunotherapy of NSCLC.

The present disclosure is directed towards genetically engineered TCR-T cells to recognize tumor antigens and simultaneously secrete a binding protein that blocks an immune checkpoint molecule and TGFβ. These engineered T cells demonstrate stronger antitumor response and reduced T cell exhaustion. The present disclosure provides immunotherapy against HPV- or EBV-positive cancers, among others.

The presently claimed and described technology provides vaccine compositions comprising at least two mutant-calreticulin (CALR)-peptides, wherein the at least two peptides have overlapping sequences and methods for administration of the vaccine compositions to induce or elicit an antitumor response or improve or enhance antitumor T cell immunity and methods of preventing, treating, reducing, or slowing progression or development of a hematological malignancy in a subject with a calreticulin mutation.

The application discloses a method for improving anti-tumor response by enhancing cellular immune response, comprising administering a nucleic acid molecule encoding an antigen membrane protein to a subject in need, wherein the antigen membrane protein is an antigen membrane protein with a front signal peptide segment removed, and belongs to the technical field of biotechnology; the method disclosed by the application enhances and accelerates the cellular immune response of a receptor, thereby improving the anti-tumor activity, and has the potential for clinical application.

The invention discloses an STAT3 mutant cell product and application thereof, and belongs to the cross technical field of genetic engineering and tumor immunotherapy. According to the application, the fact that STAT3 function acquired mutation promotes CAR-T anti-tumor reaction is found for the first time through saturated mutation screening, cell experiments and animal experiments further prove that activation of STAT3 can relieve CAR-T cell immune depletion, and the in-vivo and in-vitro killing ability of CAR-T cells on tumor cells is remarkably improved, so that the anti-tumor treatment effect is improved, and the application of the CAR-T anti-tumor drug is developed. The invention provides a new therapeutic target and therapeutic strategy for the technical field of tumor immunotherapy, and has important scientific significance and clinical application value.

Aspects herein relate to methods, compositions, and systems directed to the discovery that TSG-6 secretion by cancer-associated fibroblasts (CAFs) in a tumor, in some instances, leads to a poor response to immune checkpoint therapies in the tumor. Inhibition of TSG-6 in certain cancers, in combination with immune checkpoint therapies, led to an improved therapeutic response to the immune checkpoint therapies. Such findings provide methods and compositions for diagnosing, prognosing, and treating certain cancers.

The present invention relates to a method of preparing and expanding a population of immune cells, a potency assay for tumor recognition, a biological vaccine preparation to provide anti-tumor response or an antiviral response for cancer therapy and epitopes targets for antibodies which are useful for the construction of chimeric antigen receptors.The present invention is based on the fact that private or commonly shared tumor-associated antigens or private target antigens can be recognized by clinically relevant immune cells. Such target antigens could be used to prepare a biological vaccine preparation to provide anti-tumor response or an antiviral response by expanding a certain set of T-cells or B-cells and boosting the immune response in cancer therapy.The present invention guides the selection of viable target antigens in designing an anti-tumor vaccine to remove potentially harmful autoimmune responses or pro-tumorigenic immune responses and aids to select the biologically and clinically most relevant set of immune cells specifically directed against cancer cells harvested from tumor infiltrating lymphocytes or from different anatomical sites for the active cellular therapy of patients with cancer.

It has been discovered that the presence of cholinergic T cells is important for an effective immune response to hepatocellular carcinoma (HCC). The results demonstrate a novel aspect of the regulation of cancer immunosurveillance by an immune cell-derived neurotransmitter and shed light on its role in supporting cells mounting anti-tumor responses. Disclosed are methods of treating HCC in a subject in need thereof. Generally, the methods involve treating the subject with a therapy effective to increase the level of acetylcholine in T cells. Also disclosed are method where the subject is treated with anti-PD-1 immunotherapy when the determined level of cholinergic T cells in the subject is high or refraining from treating the subject with anti-PD-1 immunotherapy when the determined level of cholinergic T cells in the subject is low.

The present invention provides methods and compositions for conferring and / or enhancing cellular immunotherapy-mediated immune responses, such as by adoptively transferring genetically modified tumor-specific CD8+ T cells in the presence of genetically modified tumor-specific, subset-specific CD4+ T cells, wherein the CD4+ T cells confer and / or enhance the ability of the CD8+ T cells to maintain antitumor reactivity and increase and / or maximize tumor-specific proliferation of tumor-specific CD8+ T cells of interest. Also disclosed are pharmaceutical preparations made by the methods and methods of using the same.

The invention provides a method for improving TIL production quality by depriving aspartic acid to regulate immune metabolism. The method comprises an initial amplification stage and a rapid amplification stage, wherein in the later culture stage of the initial amplification stage and / or the rapid amplification stage, the cells are transferred into a deprived aspartic acid culture medium for culture until the cells of each stage are harvested. By adopting the method disclosed by the invention, the TIL multiplication capacity can be enhanced on the basis of the existing TIL amplification process, the risks of insufficient multiplication power and limited amplification in the amplification process are reduced, and a TIL amplification product meeting the feedback requirement is obtained. The method can also improve the immune effect function of an amplified final product, so that the anti-tumor immune effect of the TIL preparation for reinfusion is improved; the TIL metabolic state can be improved, the mitochondrial function can be improved, the oxidative stress level can be reduced, and the effective and continuous anti-tumor reaction can be maintained in vivo after reinfusion.