Abstract: Functional in vitro assays are provided for determining patient specific responsiveness to immunotherapy agents within a clinically actionable time frame.

Abstract: The present invention provides antigen-binding proteins capable of binding to NKp46 polypeptides. The antigen-binding proteins have increased activity in the treatment of disorders characterized by NKp46-expressing cells, particularly tumor cells.

Abstract: Antibodies specific to MUC18 (a.k.a. MCAM or CD146) and antibody-drug conjugates (ADCs) comprising such. Also provided herein are uses the the anti-MUC18 antibodies or ADCs for therapeutic and diagnostic purposes.

Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. In preferred embodiments, the antibody may be an hRS7 antibody. The methods and compostions are of use to treat Trop-2 expressing cancers in human patients, preferably in patients who are resistant to or relapsed from at least one prior anti-cancer therapy, more preferably in patients who are resistant to or relapsed from treatment with irinotecan. The immunoconjugate may be administered at a dosage of 3 mg/kg to 18 mg/kg, preferably 8 to 12 mg/kg, more preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size and reduce or eliminate metastases.

Abstract: The present invention relates to methods for producing immuno-stimulatory autologous dendritic cells. The present invention further relates to the use of such cells for treating patients suffering from hyper-proliferative disease such as cancer.

Abstract: The present disclosure relates generally to the fields of immunology and molecular biology. More specifically, provided herein are pharmaceutical combinations comprising (A) antibodies, or antigen-binding portions thereof, directed against LY75, and (B) a second anti-cancer entity; nucleic acids encoding antibody combinations; methods for preparing antibody combinations; and methods for the treatment of diseases, such as cancers mediated by LY75 expression or activity.

Abstract: The present invention relates to antibodies and fragments thereof that target the complement C3. More specifically, anti-C3 antibodies and methods of use for the treatment of various diseases or disorders are disclosed.

Abstract: The present invention provides methods for the identification of patients with an inflammatory or autoimmune disease that demonstrate an inadequate response to treatment with a multi-Fc therapeutic, and the determination of an optimal dose of a multi-Fc therapeutic for said patient based on the patient's circulating levels of inactivated C3b (iC3b) and/or additional complement components that may be employed as a surrogate for iC3b based on an analogous response to multi-Fc therapeutics. The present invention further provides for improvements in the use of such multi-Fc therapeutics in the treatment of autoimmune and inflammatory diseases.

Abstract: A pharmaceutical composition and a therapeutic method wherein an antibody-drug conjugate and an immune checkpoint inhibitor are administered in combination, and the antibody-drug conjugate is an antibody-drug conjugate in which a drug-linker represented by the following formula (wherein A represents the connecting position to an antibody) is conjugated to the antibody via a thioether bond; and a pharmaceutical composition and a therapeutic method for use in treatment of a disease that can be ameliorated through an antitumor immunity-activating effect wherein the antibody-drug conjugate is included.

Abstract: Described herein are methods of identifying immunologically protective neo-epitopes from the cancer tissue DNA of cancer patients using biophysical principles as well as bioinformatics techniques. The identification of immunologically protective neo-epitopes provides pharmaceutical compositions with a limited number of tumor-specific peptides suitable for personalized genomics-driven immunotherapy of human cancer. Specifically disclosed herein is a method of using the conformational stability of an epitope in an MHC protein-binding groove to predict immunogenicity of peptides in a putative neo-peptide set from a tumor from a cancer patient. Pharmaceutical compositions and methods of administration are also included.

Abstract: The present invention provides a method of treating a cancer in an individual using activated T cells or PBMCs induced by antigen presenting cells (such as dendritic cells) loaded with a plurality of tumor antigen peptides. The method may further comprise administration of the antigen presenting cells loaded with the plurality of tumor antigen peptides to the individual. The methods may be used singly or in combination with an immune checkpoint inhibitor. Precision therapy methods customized for the individual using neoantigen peptides or based on the mutation load in the tumor of the individual are provided. Methods of preparing the activated T cells, methods of monitoring the treatment, and methods of cloning tumor-specific T cell receptors are further disclosed. An isolated population of cells comprising the activated T cells, as well as compositions and kits useful for cancer immunotherapy are also provided.

Abstract: The present disclosure relates to, among other things, antibody-drug conjugates comprising a STING agonist cyclic di-nucleotide conjugated to an antibody, preparation methods therefor, and uses therefor.

Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to Trop-2 or CEACAM5 and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the immunoconjugate is effective to treat cancers that are refractory to or relapsed from irinotecan.

Abstract: The invention relates to the field of cell therapy, particularly NK cell mediated therapy associated with antibodies. The present invention is directed to methods and compositions for increasing the efficiency of therapeutic natural killer cells (NK cells) and/or antibodies, wherein said methods or compositions comprise the use of pooled NK cells from umbilical cord blood units (UCBs), preferably alloreactive NK cells, in combination with a therapeutic antibody in order to enhance the efficiency of the treatment in human subjects, in particularly through an increase in antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. The present invention relates to said composition as a pharmaceutical composition, preferably for its use for the treatment of a disease in a human subject in need thereof, preferably wherein said disease is a cancer, infectious or immune disease.

Abstract: Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a modified consensus MUC16 antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a modified consensus MUC16 antigen are disclosed. Methods of treating a subject with a MUC16-expressing tumor and methods of preventing a MUC16-expressing tumor are disclosed. Modified consensus MUC16 antigen is disclosed.

Abstract: Methods are provided herein for determining and administering optimized dosing of therapeutic anti-D47 agents, in a schedule that provides safe escalation of dose while achieving a therapeutic level in a clinically effective period of time. The methods can comprise the steps of clearance, escalation, and maintenance. In one embodiment the dosing regimen administers an initial (i) sub-therapeutic dose of an anti-CD47 agent or (ii) a cytoreductive therapy to achieve a safe level of circulating tumor cells for subsequent treatment (clearance); escalating the dose of an anti-CD47 agent until a therapeutic dose is reached (escalation); and maintaining the therapeutic dose for a period of time sufficient to reduce tumor cells in the bone marrow of the patient (maintenance). In an alternative dosing regimen, a patient determined to have a safe level of circulating tumor cells at presentation is treated by the steps of escalation and maintenance without initial clearance.

Abstract: Compositions disclosed herein, and methods of use thereof included those for treating or preventing sepsis in a subject in need, including methods of extending of the survival of a subject suffering from sepsis, and reduction of organ dysfunction or failure due to sepsis. Methods of treating or preventing sepsis in a subject in need includes administering compositions comprising early apoptotic cells or early apoptotic cell supernatants. Compositions and methods of use thereof may reduce the negative proinflammatory effect accompanying sepsis. In certain instances, compositions may include additional agents.

Abstract: The presently disclosed subject matter provides methods and compositions for treating myeloid disorders (e.g., acute myeloid leukemia (AML)). It relates to immunoresponsive cells bearing antigen recognizing receptors (e.g., chimeric antigen receptors (CARs)) targeting AML-specific antigens.

Abstract: The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. In preferred embodiments, the antibody may be an hRS7 antibody. The methods and compostions are of use to treat Trop-2 expressing cancers in human patients, preferably in patients who are resistant to or relapsed from at least one prior anti-cancer therapy, more preferably in patients who are resistant to or relapsed from treatment with irinotecan. The immunoconjugate may be administered at a dosage of 3 mg/kg to 18 mg/kg, preferably 8 to 12 mg/kg, more preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size and reduce or eliminate metastases.

Abstract: Engineered antibodies useful for site-specific conjugation by a transglutaminase are described. Also described are methods of site-specific conjugation of the antibodies, the site-specifically conjugated antibodies, and pharmaceutical compositions and uses related to the site-specifically conjugated antibodies.