32 results about "Adoptive cell transfer" patented technology

The present disclosure provides for methods of improving the efficacy of T cells. In an aspect, the disclosure further provides for methods of enhancing the persistence of T cells for adoptive cell transfer or therapy (ACT). Cytokine sensitivity assays (CSA) and associated methodology capable of predicting the persistence of adoptively infused T Cells are further provided for by way of the instant disclosure. The disclosure also provides for methods of treating cancer in a subject in need thereof as well as T cells populations produced by methods described herein.

The present invention relates to modulation of the tumor microenvironment to increase cancer specific immune responses. Conjugates, nanoparticles and formulations of the present invention relieve the inhibitory effect induced by tumor cells, and enhance antitumor immunity. The compostions provided herein can be used as immunotherapies, or as adjuvants used in conjunction with other immunotherapies such as peptide vaccines, cell vaccines and / or adoptive T cell transfer.

Methods for the ex vivo generation of cells of the innate (NKT cells and NK cells) and adaptive (T cells) immune systems for use in adoptive cell transfer (ACT) are provided. The NKT cells render T cells resistant to immune suppression (e.g. they are resistant to the effects of myeloid-derived suppressor cells (MDSCs)). The method involves culturing disease-primed immune cells (obtained from a cancer patient or from a patient with an infectious disease) with i) bryostatin and ionomycin (B / I) to activate and differentiate the cells; followed by sequentially culturing the cells with a) a combination of IL-7 and IL-15 and then b) IL-2, to further differentiate the cells and to render them immune resistant. The resistant immune cells are used to treat and prevent cancer and infectious diseases.

Provided are compositions and methods for enhancing immune responses to an antigen. The compositions contain an isolated population of CD8+T cells and an inhibitor of mammalian target of rapamycin (mTOR). The method for obtaining an enhanced immune response to an antigen in an individual entails administering to the individual the antigen and an inhibitor of mammalian target of rapamycin (mTOR). CD8+T cells may also be used for adoptive cell transfer (ACT) therapy.

Disclosed herein are chimeric antigen receptor (CAR) polypeptides, which can be used with adoptive cell transfer to target and kill cancers, that comprise a co-stimulatory signaling region having a mutated form of a cytoplasmic domain of CD28 that enhances CAR-T cell function, e.g. by reducing CAR-T cell exhaustion. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, which are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a tumor associated antigen-expressing cancer that involvesadoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

A method for predicting whether a patient will be a long-term survivor on treatment of a disease by adoptive cell transfer (ACT), is disclosed comprising: (i) analyzing a blood-derived sample obtained from the patient for one or more prognostic markers of long-term survival on treatment of a disease by ACT, and; (ii) based on the analysis of step (i), predicting whether the patient will be a long-term survivor on treatment of the disease by ACT. Also disclosed are methods for treating a patient by ACT, methods for selecting a patient for treatment by ACT, and methods for selecting a patient for treatment of a disease by ACT.

The present invention provides a polypeptide having the formula: St-R1-S1-Q-S2-R2 wherein St is a stalk sequence which, when the polypeptide is expressed at the surface of a target cell, causes the R and Q epitopes to be projected from the cell surface; R1 and R2 are a Rituximab-binding epitopes each having the an amino acid sequence selected from the group consisting of SEQ ID No. 1, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16 or a variant thereof which retains Rituximab-binding activity; S1 and S2 are optional spacer sequences, which may be the same or different; and Q is a QBEnd1O-binding epitope having the amino acid sequence shown as SEQ ID No. 2 or a variant thereof which QBEnd1O-binding activity. The invention also provides a nucleic acid sequence encoding such a polypeptide and uses thereof in adoptive cell transfer.

The present invention relates to a method for the absolute quantification of naturally processed HLA-restricted cancer peptides, i.e. the determination of the copy number of peptide(s) as presented per cell. The present invention can not only be used for the development of antibody therapies or peptide vaccines, but is also highly valuable for a molecularly defined immuno-monitoring, and useful in the processes of identifying of new peptide antigens for immunotherapeutic strategies, such as respective vaccines, antibody-based therapies or adoptive T-cell transfer approaches in cancer, infectious and / or autoimmune diseases.

The present invention relates to a method for the absolute quantification of naturally processed HLA-restricted cancer peptides, i.e. the determination of the copy number of peptide(s) as presented per cell. The present invention can not only be used for the development of antibody therapies or peptide vaccines, but is also highly valuable for a molecularly defined immuno-monitoring, and useful in the processes of identifying of new peptide antigens for immunotherapeutic strategies, such as respective vaccines, antibody-based therapies or adoptive T-cell transfer approaches in cancer, infectious and / or autoimmune diseases.

Embodiments of the disclosure concern engineered auto / allo-immune defense receptor (ADR)-expressing T cells that selectively target activated T cells, including pathogenic T cells, to incapacitate them. The chimeric receptors comprise moieties for targeting 4-1BB, 0X40, and CD40L, for example, whose expression is indicative of activated T cells. In particular embodiments, there are methods of preventing or treating conditions associated with activated T cells using adoptive T-cell transfer of cells encoding the ADRs.

The present invention generally relates to methods of preparing leukocytes, particularly T cells, ex vivo for use in immunotherapy, particularly cancer immunotherapy. More specifically, the invention relates to methods for the preparation of leukocytes exhibiting cytotoxic properties for use in adoptive cell transfer. The invention also relates to cells and compositions including them for cancer immunotherapy. The invention also relates to methods of immunotherapy, particularly cancer immunotherapy. The present invention relates to a method for producing a leukocyte that has an enhanced capacity for killing a target cell, the method including contacting the leukocyte with a PTPN2 inhibitor in conditions for enabling the inhibitor to inactivate PTPN2 in the leukocyte, thereby producing a leukocyte that has an enhanced capacity for killing a target cell. Preferably, the leukocyte is contacted with the PTPN2 inhibitor in the absence of a T helper cell.

Embodiments of the disclosure concern engineered auto / allo-immune defense receptor (ADR)-expressing T cells that selectively target activated T cells, including pathogenic T cells, to incapacitate them. The chimeric receptors comprise moieties for targeting 4-1BB, OX40, and CD40L, for example, whose expression is indicative of activated T cells. In particular embodiments, there are methods of preventing or treating conditions associated with activated T cells using adoptive T-cell transfer of cells encoding the ADRs.

The present disclosure relates generally to polypeptides, cells, compositions and methods for enhancing immune function, and in particular the immune function of T cells, such as CD8+ T cells. More particularly, the present invention relates to modified DNAM-1 polypeptides, T cells expressing recombinant and / or modified DNAM-1, and methods of using these cells in adoptive T cell transfer, such as for the treatment of cancer or infection. The disclosure also relates to methods for preparing T cells with enhanced immune function; methods for preparing T cells for adoptive cell therapy; methods for assessing the immune function of T cells in a subject or cell population; methods for predicting the responsiveness of a subject with cancer to cancer therapy; and methods for predicting the survival or survival time of a subject with cancer.

The present disclosure includes compositions, methods, and uses for a subset of T cells, SP T (TSP) cells, which display a quiescent (G0) phenotype. Aspects of the disclosure include methods for obtaining and mobilizing TSP cells in a subject. Other aspects include methods of adoptive cell transfer in a subject utilizing TSP cells.

Provided herein are methods and compositions useful for treating PDL1 and / or PDL2 positive cancers through adoptive cell transfer of T cells genetically engineered to express a PD1-specific chimeric antigen receptor. Co-stimulatory domains such as Dap 10 may be included to enhance efficacy.

The present disclosure provides for methods of improving the efficacy of T cells. In an aspect, the disclosure further provides for methods of enhancing the persistence of T cells for adoptive cell transfer or therapy (ACT). Cytokine sensitivity assays (CSA) and associated methodology capable of predicting the persistence of adoptively infused T Cells are further provided for by way of the instant disclosure. The disclosure also provides for methods of treating cancer in a subject in need thereof as well as T cells populations produced by methods described herein.

The present invention describes a method for treating cancer comprising adoptive transfer of tumor antigen specific CD8+ T cells and an oncolytic virus vaccine targeting the same antigen.

Cell loss by apoptosis is a common feature in certain conditions, including cancer. Dying tumor cells induce immune tolerance within the tumor microenvironment largely through highly conserved homeostatic clearance programs that are designed to restore tissue homeostasis and contribute to the formation of an immunosuppressive niche. The translocation of phosphatidylserine (PS) on cellular membranes, during the initial phases of apoptosis, functions as a recognition and removal signal that limits the immunogenicity of cell death. To remove inhibitory signals in the homeostatic clearance pathway a fusion protein comprising a phosphatidylserine binding domain and an immunostimulatory domain can restore immune responses to dead tumor cells in antigen cross presentation assays and promotes recruitment and retention of tumor antigen specific immune effector cells into tumors. These effects combine to elicit anti-tumor immunity, improve responses to immune checkpoint inhibitors, and enhance the effectiveness of adoptive T cell transfers using engineered T cells.