36 results about "Cytolysis" patented technology

Methods for selecting a cancer patient for immunotherapy comprise establishing a total passenger gene mutation burden from a tumor of a cancer patient, generating a background distribution for the mutational burden of the tumor, normalizing the total passenger gene mutation burden against the background distribution, and categorizing the cancer patient as an immunotherapy responder when the total passenger gene mutation burden is greater than the mean of the background distribution. When the cancer patient is an immunotherapy responder, the patient may be administered an immunotherapy regimen that comprises activation / inhibition of T cell receptors that promote T cell activation and / or prolong immune cytolytic activities.

The present invention relates to activatable recombinant polypeptide compositions comprising a cleavage release segment. In some instances, the activatable recombinant polypeptide compositions include an XTEN linked to binding moieties by cleavable release segments that, when cleaved, the binding moieties are capable of binding together effector T cells with targeted tumor or cancer cells and effecting cytolysis of the tumor cells or cancer cells. The invention also provides compositions and methods of making and using the cleavable activatable recombinant compositions.

The application belongs to the technical field of microbial fermentation, and particularly relates to a kind of cytolysis product of mixed bacteria fermentation and a preparation method. The cytolysis product is prepared by mixed bacteria fermentation of two kinds of aerobic probiotics, i.e. Lactobacillus plantarum and Aspergillus oryzae are used as fermentation strains to carry out mixed bacteria fermentation treatment on rice milk, and membrane filtration and column chromatography system are used for filtration and enrichment, so as to obtain a cytolysis fermentation product filtrate rich in kojic acid, the content of kojic acid is greater than 200 g / L, which is significantly improved compared with conventional process. The obtained cytolysis product has no bad smell and clear color, so that the beneficial function of kojic acid can be played only with a low addition amount in cosmetics, and the addition of odor masking and color correcting auxiliaries is reduced, and the cytolysis product can be used for preparing cosmetics with skin repair, whitening and other functions.

Provided herein are engineered halotolerant microorganisms that are susceptible to cell lysis upon resuspension in distilled water, the process of engineering the halotolerant microorganisms, and the uses thereof, including for the recovery of biomacromolecules.

Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g. anti-PD1 antibody) could efficiently repress tumor growth in human cancer. The present invention also relates to multispecific antibodies comprising at least one binding site that specifically binds to an immune checkpoint molecule (e.g. PD-1), and at least one binding site that specifically binds to NRP-1. The present invention also relates to a population of cells engineered to express a chimeric antigen receptor (CAR) and wherein the expression of NRP-1 in said cells is repressed.

Several embodiments disclosed herein relate to the compositions comprising engineered Natural Killer (NK) cells that express a chimeric receptor, the chimeric receptor imparting to the NK cells an enhanced ability to target specific cells, such as cancerous cells or those affected by an infectious disease. Several embodiments relate to NK cells that target cells expressing natural ligands of NKG2D, where the NK cells comprise transmembrane and / or signaling domains that lead to cytotoxic and / or cytolytic effects when the NK cells bind a target cell. Uses of NK cell compositions to treat diseases are also provided for in several embodiments.

To provide an anti-C5 antibody for treatment of neuromyelitis optica spectrum disorder.SOLUTION: Provided are methods for clinical treatment of neuromyelitis optica spectrum disorder (NMOSD) using an anti-C5 antibody, or antigen binding fragment thereof. The present disclosure provides a method of treating neuromyelitis optica spectrum disorder (NMOSD) in a subject in need thereof by administering an antibody that specifically binds to a complement component 5 (C5). In certain embodiments, the antibody that specifically binds to the C5 reduces a rate at which the C5 is cleaved in vivo into C5a and C5b. In other embodiments, the antibody that specifically binds to the C5 binds to one or both of the C5a and / or C5b fragments. In any of these embodiments, the antibody that specifically binds to the C5 reduces a complement cascade at the C5, thereby reducing release of proinflammatory mediators and formation of a cytolytic pore.SELECTED DRAWING: None

The present invention provides a chimeric antigen receptor (CAR) which binds a low density target antigen, which comprises a Fab antigen binding domain. The invention also relates to cells expressing such a CAR and their use in the treatment of disease.

The present disclosure provides a method for treating cancer, which includes, inter alia, a) an intratumoral cell lysis step mediated by cryolysis, and b) an intratumoral administration step of a combination of immunotherapeutic agents including: 1) i) a TLR9 agonist CpG oligodeoxynucleotide, ii) an agonistic anti-CD40 monoclonal antibody, iii) an agonistic anti-OX40 monoclonal antibody, and iv) an anti-CTLA4 monoclonal antibody, or 2) i) a TLR9 agonist CpG oligodeoxynucleotide, ii) an agonistic anti-CD40 monoclonal antibody, iii) an anti-PD1 monoclonal antibody, and iv) an anti-CTLA4 monoclonal antibody.

To provide anti- CD3 antibodies that more closely mimic TCR / MHC interactions and are desirable for minimizing the release of toxic cytokines while maintaining effective tumor cytolysis.SOLUTION: Novel human CD3 antigen binding polypeptides and their preparation and their use in the treatment and / or diagnosis of various diseases, as well as bispecific antibody molecules capable of activating immune effector cells and their use in the diagnosis and / or treatment of various diseases. In some embodiments, the anti-CD3 antibody is characterized or selected to have a reduced tendency to induce cytokine release upon binding to a competent T cell, e.g., due to the release of IL-2 and IFN γ.SELECTED DRAWING: Figure 1

The invention discloses an anti-CD20 antibody or an antigen binding fragment binding to CD20 and application of the anti-CD20 antibody or the antigen binding fragment binding to CD20. After the anti-CD20 antibody and the CD20 antigen binding fragment disclosed by the invention are specifically bound with a CD20 antigen on a cell, immune response is started to mediate B cell dissolution, so that the growth of tumor cells is effectively inhibited or the tumor cells are cleared, and the anti-CD20 antibody and the CD20 antigen binding fragment have a good patent medicine prospect.

Methods and systems for rapid preparation of nucleic acid samples.

The present invention relates to a therapeutic combination of a BTN3A-activating antibody, a Bcl-2 family inhibitor and a demethylating agent, which is useful, inter alia, in the treatment of cancer, in particular hematological malignancies. The present disclosure more particularly relates to the combined use of BTN3A-activating antibodies that activate the cytolytic function of V [gamma] 9V [delta] 2T cells, WiNtural that selectively inhibits the Bcl2 receptor, and a demethylating agent, such as azacitidine, to synergistically and specifically promote the anti-cancer activity of V [gamma] 9V [delta] 2T cells.

A combination therapeutic strategy employs multiple oncolytic viruses (OVs), grouped and administered based on their virological properties, tumor selectivity, and distinct antigen profiles, to treat malignant tumors. Representative groupings may include members of flaviviruses, each contributing distinct immune modulation and the same modes of tumor cell killing. A predefined treatment schedule involves sequential or concurrent administration of antigenically diverse OVs in multiple cycles, reducing cross-neutralization and sustaining cytolytic pressure on tumors. A pre-characterized OV panel, comprising members from a virus family, RNA and DNA viruses, both wild-type and genetically engineered, serves as a flexible resource for customizing treatment regimens by tumor type, immune landscape, and therapeutic goals. This platform establishes a rational framework for combination OV therapy with improved durability, safety, and clinical effectiveness.

The present application relates to therapeutic combinations of BTN3A-activating antibodies and immune checkpoint inhibitors selected from LAG-3 inhibitors (anti-LAG-3 antibodies and LAG-3 fusion proteins), anti-TIGIT antibodies or anti-TIM-3 antibodies, which are particularly useful in the treatment of cancer. The present disclosure more specifically relates to the combined use of a BTN3A-activating antibody that specifically binds to BTN3A and activates the cytolytic function of V9V2T cells, and a LAG-3 inhibitor that can bind directly to a LAG-3 molecule or a ligand thereof, block the interaction between LAG-3 and its ligand, to promote a synergistic anti-tumor effect.

The present invention relates to a stem cell in which FTO gene expression is suppressed, an immune cell differentiated therefrom, and a use thereof. In the present invention, it is found that inhibition of FTO gene expression in immune cells significantly improves cytolytic activity, and immune cells differentiated from stem cells in which FTO gene expression is inhibited exhibit excellent cytolytic activity against cancer cells, thereby overcoming the limitations of existing immune cell therapies. For example, immune mismatch and cell number are limited. Furthermore, in the present invention, the CAR gene is introduced into the position of the FTO gene in the stem cell to produce a stem cell in which the FTO gene is deleted and the CAR gene is simultaneously expressed. Immune cells differentiated from stem cells exhibit significantly excellent cytolytic activity with respect to cancer cells. Therefore, the present invention can be effectively used as an immune anti-cancer cell therapeutic agent.

Evaluation of immune cells and cancer cells is provided by assessing cytolysis of cancer cells by effector cells, comprising: a) providing a cell-substrate impedance monitoring device operably connected to an impedance analyzer, the device including a well for receiving cells and an electrode array in the bottom of the well, and further operably connected to an imaging unit; b) adding target cells characterized as cancer cells to the well; c) disposing a layer comprising extracellular matrix (ECM) over the target cells; d) adding effector cells on top of the ECM layer; and e) imaging the well and monitoring the cell-substrate impedance of the well to determine invasion of the effector cells through the ECM layer and the effectiveness of the effector cells in killing the target cells directly or via migration and invasion through the extracellular matrix.

Evaluating immune and cancer cells is provided for by assessing cytolysis of cancer cells by effector cells, which includes: providing a cell-substrate impedance monitoring device operably connected to an impedance analyzer, wherein the device comprises a well for receiving cells and an electrode array at a base of the well, the device further operably connected to an imaging unit; b) adding target cells characterized as cancer cells to the well; c) disposing a layer comprising an extracellular matrix (ECM) over the target cells; d) adding effector cells over the ECM layer; and e) imaging the well and monitoring cell-substrate impedance of the well to determine invasion of the effector cells through the ECM layer and effectiveness of effector cell killing of the target cells either directly or via migration and invasion through extracellular matrix.

The present invention relates to a modified immune cell for use in the treatment of a solid tumor in a subject wherein the modified immune cell comprises one or more exogenous nucleic acid molecules encoding a transgenic construct targeting an antigen expressed in a cancer cell of said solid tumor, in said immune cell, nuclear receptor subfamily group 2 F member 6 (NR2F6) activity is suppressed (as compared to a control immune cell), and binding of the immune cell to an antigen is associated with death of the cancer cell expressing the antigen, and inducing a secondary immune response against a cancer cell of a solid tumor in a subject, the secondary immune response is non-specific (epitope diffusion) for the antigen targeted to the transgenic construct. The present invention also relates to a modified immune cell comprising one or more exogenous nucleic acid molecules encoding a transgenic construct targeting an antigen expressed in a cancer cell of a solid tumor in which NR2F6 activity and Casite B line lymphoma oncogene-b (CBLB) activity are inhibited (as compared to a control immune cell). The invention also relates to pharmaceutical compositions comprising a modified immune cell suitable for the treatment of solid tumors, additionally comprising a pharmaceutically acceptable carrier, and to in vitro methods for enhancing the cytolytic activity of the modified immune cell.

The present invention relates to engineered a cytolytic immune cell comprising: i) a releasable protein which comprises a polypeptide of interest (POI) and a first interaction domain; and ii) a retention protein which is retained within an intracellular compartment of the cell and comprises a second interaction domain which binds to the first protein interaction domain, wherein binding between the first protein interaction domain and second protein interaction domain is disrupted by the presence of an agent, such that in the absence of the agent, the first protein interaction domain and second protein interaction domain bind and result in retention of the POI within an intracellular compartment; whereas in the presence of the agent, the first protein interaction domain and second protein interaction do not bind and the POI is released from the intracellular compartment and expressed at the cell surface or secreted by the cell.

A method is provided for assessing immune cells and cancer cells by assessing cytolysis of cancer cells by effector cells, the method comprising: providing a cell-substrate impedance monitoring device operably connected to an impedance analyzer wherein the device comprises a well for receiving cells and an electrode array at a base of the well, the apparatus is further operably connected to the imaging unit; b) adding target cells characterized as cancer cells into the pores; c) disposing a layer comprising an extracellular matrix (ECM) over the target cells; d) adding effector cells over the ECM layer; and e) imaging the well and monitoring the cell-substrate impedance of the well to determine the invasion of the effector cell through the ECM layer and the effectiveness of the effector cell to kill the target cell either directly or via migration and invasion through an extracellular matrix.

The invention relates to a biotechnological process which comprises a bead milling step and / or an alkaline treatment step (process step a), and / or a subsequent enzymatic treatment step (process step b) and a cytolysis step (process step c) taking place after process step a) and / or after process step b). The invention further relates to the use of the components obtained by the biotechnological process as a nutrient composition, food product, food additive, pharmaceutical ingredient or nutrient medium for cell cultures.

Disclosed is a method and device / apparatus for determination of the contribution from lysed cells to measurement values of an analyte present in the extracellular compartment. The method employs multiple tandem measurements of analyte and an intracellular marker from samples where different numbers of cells are lysed so as to establish the relationship between the measured value of the intracellular marker and the analyte.

This application relates to therapeutic combinations of BTN3A-activating antibodies with immune checkpoint inhibitors selected from LAG-3 inhibitors (anti-LAG-3 antibodies and LAG-3 fusion proteins), anti-TIGIT antibodies, or anti-TIM-3 antibodies, which are particularly useful for treating cancer. More specifically, this disclosure relates to the combination of BTN3A-activating antibodies that specifically bind to BTN3A and activate the cytolytic function of Vy9V52 T cells with LAG-3 inhibitors that can directly bind to LAG-3 molecules or their ligands and block the interaction of LAG-3 with these ligands to promote a cooperative anti-tumor effect.

Provided herein are methods of isolating intracellular products (e.g., viral particles or nucleic acid molecules) from a cell suspension. Also provided herein are methods of mechanically lysing cells. In some embodiments, provided herein are methods of mechanically lysing cells to isolate intracellular products (e.g., viral particles or nucleic acid molecules) from a cell suspension. Also provided herein are instruments and cartridges for use in mechanical lysis of cells.

Provided is a method with which it is possible to easily measure lysosomal activity of cells in a sample. A method for measuring the activity of lysosome in a cell in vitro, said method comprising the following steps (1)-(4): (1) a step for culturing a cell by adding a fluorescent substance-binding protein to a cell-containing medium; (2) a step for collecting the cultured cells after step (1); (3) a step for adding a composition for cell lysis to the cultured cells collected in step (2) to obtain a cell lysate component; and (4) a step for measuring the fluorescence intensity of the fluorescent substance-bound protein in the cell lysate component obtained in step (3).

The disclosure provides, in various embodiments, polynucleotides and vectors comprising sequences encoding a mono-specific or a bi-specific CAR that is capable of binding to a first TAA, or a T-cell engager that is capable of binding to CD3 and a second TAA, or a combination thereof. The disclosure also provides, in various embodiments, T lymphocytes comprising one or more of the polynucleotides or vectors; compositions (e.g., pharmaceutical compositions) and kits comprising one or more of the T lymphocytes; methods of treating a cancer in mammalian subject (e.g., a human), and methods of inducing T cell-mediated cytolysis of cancer cells (e.g., solid tumor cells).

The disclosure is generally related to nanoparticles have an oxidized tumor cell lysate encapsulated therein and oligonucleotides on the surface thereof. Methods of making and using the nanoparticles are also provided herein.