Abstract: In the present disclosure, polymer conjugates, including polymer-antibody-drug conjugates (polymer ADCs) are described, as well as the use of such conjugates to treat human disease. The polymer conjugates can contain a large number of polymer-bound agents, thus effectively increasing the drug antibody ration (DAR) of the antibody significantly beyond the currently available technology. This may be of particular importance when antibodies to low density antigens are used as target antibodies. The described polymer-ADCs have improved pharmacokinetics and solubility relative to traditional ADCs. The linker between agent and the polymer can be tailored to provide release of toxin at the desired site and under the desired conditions within the tumor. An additional feature of the polymer-ADCs of the current disclosure is that a purification moiety can be attached to the polymer backbone to provide ease of purification of the polymer-ADCs.

Abstract: The invention relates to therapeutic conjugates with improved ability to target various cancer cells containing a targeting moiety and a therapeutic moiety. The targeting and therapeutic moieties are linked via an acid cleavable linkage that increases therapeutic efficacy of the immunoconjugate.

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 present invention relates to a labeled chimeric non-therapeutic antibodylike protein comprising, in a hypervariable region thereof, an enzyme cleavable peptide sequence derived from a hypervariable region of a reference therapeutic antibody.

Abstract: Disclosed herein are methods of increasing numbers of monocytes to a tumor or cancer metastasis site in a subject. Non-limiting embodiments include administering or using a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+ GR1? (Ly6C?)) monocytes; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1? (Ly6C?)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist. Also disclosed herein are methods of increasing, stimulating, activating or promoting monocyte migration to or mobilization against a tumor or cancer metastasis in a subject. Non-limiting embodiments include administering a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1? (Ly6C?)) monocytes; or CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1? (Ly6C?)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist.

Abstract: The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. The ADC may be administered at a dosage of between 4 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, most preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC 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. Preferably, the ADC is administered in combination with one or more other therapeutic agents, such as a PARP inhibitor, a microtubule inhibitor, a Bruton kinase inhibitor or a PI3K inhibitor. Most preferably, the ADC is of use for treating a Trop-2 expressing cancer, such as metastatic urothelial cancer.

Abstract: A combination which comprises an effective amount of Her2/Neu antagonist and an effective amount of immunotherapeutic that is capable of activating a human plasmacytoid dendritic cell, myeloid dendritic cell, NK cell, or a combination thereof is disclosed.

Abstract: Isolated or recombinant monoclonal antibodies that bind to GARP are provided. In some cases, antibodies of the embodiments can be used for the detection, diagnosis and/or therapeutic treatment of human diseases, such as cancer. Further provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of an anti-platelet agent and a T cell therapy.

Abstract: The present invention provides chimeric antigen receptor (CAR)-T cells modified to express a CAR fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising VH and VL, wherein scFv has an activity against a tumor antigen CD19, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain; wherein the fusion protein further comprises a FLAG tag N-terminus to scFv, C-terminus to scFv, or between VH and VL. Using CD19-FLAG CAR-T cells instead of CD19 CAR-T cells, cytokine levels (Interferon-?, IL-2 and IL6) caused by infused CAR-T cells are reduced.

Abstract: The present invention concerns a pharmaceutical composition where a checkpoint inhibitor is combined with an oncolytic virus and the use of said combination for the treatment of cancer.

Abstract: Disclosed herein is a different and novel approach to cancer vaccines using a subject's own dendritic cells (DCs) and macrophages (Mphs) in combination to present cancer antigens to the immune system. Further disclosed are methods of producing monocyte-derived autologous DCs and Mphs loaded ex vivo with particular whole irradiated cancer cells which generates optimally activated immunostimulatory antigen-presenting cells (APCs) as a superior method for stimulating robust and long-lasting immunity to a particular cancer in vivo as compared with more traditional vaccination methods. Compositions, methods of use and methods for preparation of these DCs and Mphs with cancer cells are also disclosed herein.

Abstract: The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

Abstract: A method for identifying T-cell epitopes which can be used to elicit T cells targeting cells capable of regenerating cancers is disclosed. The method identifies T-cell epitopes with a high curative potential, high potency and high probability of T cell recognition (HP). The method includes: (i) identifying high curative potential tumor protein target i.e., identifying HP-TP; (ii) identifying peptide sequences within the protein sequence of an HP-TP that have a high probability of eliciting T cell killing; and (iii) qualifying the sequence specificity based on the fold difference between the specific target and non-targets. The identified T-cell epitopes include a core sequence of 9 amino acids homologous to a sequence expressed within a qualified HP-TP. The T-cell epitopes can be used in a method for reprograming T cells to selectively attack tumor cells capable of perpetuating a tumor and treating patients, for example, cancer patients.

Abstract: The present disclosure provides synthetic antibodies specific for a disease-associated antigen, and methods of using the antibodies in disease therapy. The present disclosure further provides diagnostic assays involving detecting the presence and/or level in biological sample of an antibody specific for a disease-associated antigen.

Abstract: Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, methods of treating a cancer or tumor, methods of reducing tumor load, methods of reducing the size or growth rate of a cancer or a tumor, and methods of extending of the survival of a subject suffering from a cancer or tumor, wherein the subjects are administered compositions comprising apoptotic cells or apoptotic cell supernatants. Compositions and methods of use thereof may increase the efficacy of a CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm. In certain instances compositions may include additional chemotherapeutic or immunomodulatory agents.

Abstract: The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a CD20-expressing cancer.

Abstract: The present invention relates to combination therapy with drugs, such as Bruton's tyrosine kinase inhibitors or PI3K inhibitors, with antibodies or ADCs against HLA-DR. Where ADCs are used, they preferably incorporate SN-38 or pro-2PDOX. The ADC may be administered at a dosage of between 1 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. The combination therapy 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. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

Abstract: Provided is 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. Also provided are precision therapy methods customized for the individual using neoantigen peptides or based on the mutation load in the tumor of the individual, methods of preparing the activated T cells, methods of monitoring the treatment, methods of cloning tumor-specific T cell receptors, an isolated population of cells comprising the activated T cells, and compositions and kits useful for cancer immunotherapy.

Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

Abstract: A pharmaceutical composition contains an antibody or a fragment thereof specific for COL6A3 for the treatment of a cancer. A method of treating a cancer includes administering to a subject in need thereof the pharmaceutical composition. A kit includes a container that contains the pharmaceutical composition. A method of producing an antibody or a fragment thereof against a peptide or a MHC/peptide complex. A method for detecting a diseased tissue includes administering to a subject in need thereof an antibody or a fragment thereof conjugated to a radioisotope and detecting a signal from the radioisotope in the subject. A method for treating a diseased tissue includes administering to a subject in need thereof an antibody or a fragment thereof conjugated to a toxin.