24 results about "B cell malignancy" patented technology

Provided are adoptive cell therapy methods involving the administration of doses of cells for treating B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with chronic lymphocytic leukemia (CLL). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods involve prior administration of a lymphodepleting therapy, such as prior administration of fludaribine and / or another lymphodepleting chemotherapeutic agent, for example cyclophosphamide. In some embodiments, features of the methods include an increase in complete remission, overall survival and / or progression free survival of subjects treated in accord with the provided methods.

The present disclosure provides combinations of anti-CD19 agents and B cell targeting agents and methods of treating subjects having B cell malignancies with combinations of anti-CD19 agents and a B cell targeting agents.

The present invention relates to the field of T cells and provides methods of producing autologous T cells and compositions thereof for the treatment of B-cell malignancies and other cancers. A method of making T cells expressing a cell surface receptor that recognizes a specific antigen moiety on the surface of a target cell, the method comprising enriching a population of lymphocytes; stimulating the population of lymphocytes with one or more T cell stimulators to produce a population of activated T cells, the stimulation being performed in a closed system using a serum-free culture medium; transduction of the activated population of T cells with a viral vector comprising a nucleic acid molecule encoding a cell surface receptor, producing a transduction population of T cells using single cycle transduction, the transduction being performed in a closed system using a serum-free culture medium; the transduced population of T cells is expanded for a predetermined time resulting in an engineered population of T cells, the expansion being performed in a closed system using a serum-free culture medium. The methods and processes described herein can be completed in significantly shorter time.

Provided are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods are for treating subjects with relapsed or refractory NHL. Also provided are articles of manufacture and prophylactic treatments in connection with adoptive therapy methods.

The present disclosure relates to dosage regimes of anti-CD19 agents, in particular an anti-CD19×anti-CD3×anti-CD2 trispecific agent administered intravenously (i.v.) and subcutaneously (s.c.), and their use for treating diseases and disorders associated with expression of CD19 such as B cell malignancies, in particular relapsed and / or refractory B-cell malignancies.

The present invention is directed to the field of immunotherapy, in particular, adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer, in particular, of B cell lymphoma or B cell leukemia. The invention provides a nucleic acid encoding TCR alpha or beta chain constructs of TCR constructs capable of specifically binding to a peptide of SEQ ID NO: 1, derived from the lineage specific antigen CD22, in the context of HLA-A2 and to subsequently lyse CD22-positive cells. The invention further provides a corresponding protein and host cell. e.g., a CD8+ T cell, pharmaceutical compositions comprising the same, and therapeutic use for treatment of B cell lymphoma or B cell leukemia, such as diffuse large B-cell lymphoma (DLBCL).

Adoptive cell therapy, and related methods, compositions, uses, and articles of manufacture, are provided that include administration of a dose of cells for treating a subject having a particular B cell malignancy. The cells generally express a recombinant receptor, such as a chimeric antigen receptor (CAR). In some embodiments, the disease or condition is large cell type B cell lymphoma (LBCL) that is refractory or relapsed to frontline chemoimmunotherapy.

Antibodies, fragments thereof, and fusion proteins that specifically bind to CD19, as well as methods of making and using such antibodies, are described. Such antibodies, fusion proteins, and fragments thereof can be used to treat and diagnose various B cell disorders, including B cell malignancies and autoimmune diseases.

The present invention relates to the field of T cells and provides methods of producing autologous T cells and compositions thereof for the treatment of B-cell malignancies and other cancers. A method of making T cells expressing a cell surface receptor that recognizes a specific antigen moiety on the surface of a target cell, the method comprising enriching a population of lymphocytes; stimulating the population of lymphocytes with one or more T cell stimulators to produce a population of activated T cells, the stimulation being performed in a closed system using a serum-free culture medium; transduction of the activated population of T cells with a viral vector comprising a nucleic acid molecule encoding a cell surface receptor, producing a transduction population of T cells using single cycle transduction, the transduction being performed in a closed system using a serum-free culture medium; the transduced population of T cells is expanded for a predetermined time resulting in an engineered population of T cells, the expansion being performed in a closed system using a serum-free culture medium. The methods and processes described herein can be completed in significantly shorter time.

The present disclosure provides methods of treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder by administering hypoimmune allogenic CD19-directed CAR T cells. Also disclosed are pharmaceutical compositions comprising hypoimmune allogenic CD19-directed CAR T cells, for use in treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder.

Antibodies, fragments and fusion proteins thereof, that specifically bind to CD19 are described, as well as methods of making and using such antibodies. Such antibodies, fusion proteins, and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases.

A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR than can trigger T-cell activation upon detection of either CD19 or CD20 (or both). IT is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

Provided herein are methods for: (1) rapidly depleting circulating B cells and remodeling one or more B cell compartments, (2) treating B cell-related autoimmune diseases, and (3) B cell malignancies, using B cell depleting antibodies that are directed to CD19 or CD20 and one or more target antigens. Further provided herein is a CD19 / CD20 bispecific antibody with dual Fc domains that mediate enhanced effector functions and B cell depletion. HB2198 demonstrated enhanced binding to Fcγ receptors, potent effector functions, and efficient depletion of B cells in vitro and in vivo.

Embodiments described here are directed to novel methods for detecting commensal bacteria-specific antibodies, such as commensal bacteria-specific immunoglobulin antibodies, in a blood sample or tissue fluid from a subject suspected of or suffering from a B cell malignancy, where the methods are for early detection or diagnosis of B cell malignancies and for early detection of relapse or recurrence of a B cell malignancy in remission patients previously diagnosed as suffering from a B cell malignancy. Also, described are embodiments directed to apparatuses for use with the novel methods described here. Methods of treating a subject suspected of or suffering from a B cell malignancy or a relapse or a recurrence of a B cell malignancy that can be used in combination with or without the methods of detecting commensal bacteria-specific antibodies and / or standard of care treatment are also provided here.

The present invention provides to develop novel chimeric antigen receptor (CAR) encoded by an open reading frame 3 (ORF3) mRNA and amino acid sequences of any one of SEQ ID NO: 1 to SEQ ID NO: 109 specific to CD19 against hematologic malignancies associated with expression of Cluster of Differentiation 19 (CD19). The invention relates to the design of a synthetic CAR mRNA sequence comprising hu anti CD19 scFv, a hinge, a Transmembrane domain, a co-stimulatory domain and a CD3ζ signaling domain, where with the costimulatory is CD27 or 41BB for targeting and destroying malignant B-cells. This disclosure features anti-CD19 CAR T-cell therapy for antigen binding domains, directed to B cell malignancies, described herein.

The invention belongs to the technical field of tumor immune drugs, and provides a preparation method and application of a CD19 and CD20 targeted double-target CAR-T cell, a CD19 and CD20 targeted CAR sequence is used, a combined structure of an antigen recognition domain and a hinge region is optimized, and the CD19 and CD20 targeted double-target CAR-T cell is obtained. Three groups of double-target CAR-T cells, namely, CAR2019-01, CAR2019-02 and CAR2019-03, are prepared by adopting a lentivirus transduction technology, and two groups of single-target CAR-T cells, namely, CAR19 and CAR20, are used as contrasts; the CAR-T cell comprises an antigen recognition domain, a hinge region, a transmembrane structural domain, a 4-1 BB costimulatory factor and a CD3 zeta intracellular signal domain, the double-target design is that scFv of CD19 / CD20 is connected in series through an (EAAAK) * 3 linker, the killing effect of the double-target CAR-T cell on blood system tumors is remarkably better than that of a single-target CAR-T cell, and CAR2019-03 shows a more excellent anti-tumor function than other two double-target CAR-T cells, so that the CAR-T cell can be used for preparing a medicine for treating tumors. The CAR-T cell drug is suitable for preparing the CAR-T cell drug for treating the recurrent / refractory B-cell malignant tumor.

The invention discloses application of a Bruton's tyrosine kinase inhibitor. The invention belongs to the technical field of medicines, and particularly relates to application of a compound shown as a formula (I) or pharmaceutically acceptable salt, isomer or crystal form thereof in preparation of medicines for preventing or treating B-cell malignant tumors.

The application belongs to the field of biotechnology and immunotherapy, and particularly relates to an additive composition for enhancing the killing activity of CAR-CD19 T cells on B cell malignancies, a culture medium and application thereof. The composition is composed of SIRT1 activator SRT2104 and antioxidant ergothioneine, and the final concentrations of the two in the T cell culture medium are 1-10 muM and 5-50 muM respectively. In vitro killing experiments show that the killing efficiency of the composition on Nalm6 tumor cells is significantly better than that of SRT2104 or ergothioneine alone, and the composition has a significant synergistic effect, thereby providing a new solution for improving the CAR-T cell immunotherapy effect.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express cytotoxic chimeric receptors and various dosing regimens for administering such cells. In several embodiments, the immune cells express a chimeric receptor that targets CD19 on tumor cells. In several embodiments, the cancer is a blood cancer, for example, B cell malignancy. In several embodiments, the immune cells engineered to express a CD 19-directed CAR are administered in combination (prior to, after or concurrently) with an antibody therapy, such as an anti-CD20 directed antibody.

There is provided a chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—GY-AFSSS (SEQ ID No. 1); CDR2—YPGDED (SEQ ID No. 2) CDR3—SLLYGDYLDY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—SASSSVSYMH (SEQ ID No. 4); CDR2—DTSKLAS (SEQ ID No. 5) CDR3—QQWNINPLT (SEQ ID No. 6). There is also provided a cell comprising such a CAR, and the use of such a cell in the treatment of cancer, in particular a B cell malignancy.

Chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of B cell malignancies, but a significant proportion of patients with large B cell lymphoma (LBCL) experience primary resistance or relapse after CAR T cell treatment. As disclosed herein, anti-inflammatory macrophages suppress CAR-T cell expansion, induce death, and reduce CAR expression. Disclosed is a method for enhancing anti-tumor efficacy of immune effector cells, such as CAR-T cells, in a subject that involves administering to the subject a nitric oxide synthase (NOS) inhibitor.

Provided are adoptive cell therapy involving the administration of doses of cells for treating subjects with certain B cell malignancies, and related methods, compositions, uses and articles of manufacture. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the disease or condition is a large B cell lymphoma (LBCL) relapsed or refractory to first-line chemoimmunotherapy.

The disclosure provides chimeric antigen receptors (CARs), T cells comprising such CARs, nucleic acids that encode such CARS, and methods of use thereof, e.g., to treat cancer such as B cell malignancies.

Provided are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods are for treating subjects with relapsed or refractory NHL. Also provided are articles of manufacture and prophylactic treatments in connection with adoptive therapy methods.