Compositions and methods useful for delivery of targeted therapies for pulmonary arterial hypertension, sepsis, cancer and cachexia. The compositions and methods are based on peptide pharmacophores that selectively bind to and home to diseased tissue and enable targeted therapies to affect a beneficial therapeutic result. Peptide pharmacophores may selectively target tumor vasculature, regenerating tissue, wounded tissue, inflamed tissue, fibrotic tissue, remodeled tissue, tissue characterized by elevated heparanase levels, and have the ability to internalize into such diseased cells.

Chimeric molecules and molecule complexes that include an Fc portion of an antibody and an immunomodulatory portion and uses thereof are contemplated. Typically, the chimeric molecule comprises at least two immune effectors, for example, IL-15 antagonist and PD-L1 binding domain. It is contemplated that a tumor cell or an immune competent cell can be exposed to the chimeric molecule to increase the effectiveness tumor cell lysis via an antibody-dependent cell-mediated cytotoxicity.

The invention relates to an anti-thrombotic molecule having both anti-platelet and anti-coagulant (APAC) activity and, in particular, its use as a medicament to prevent and/or treat heparin-induced thrombocytopenia (HIT) type I or II; and/or heparin-induced thrombocytopenia and thrombosis (HITT); and/or heparin-independent thrombocytopenia autoimmune HIT (aHIT); and/or vaccine-induced thrombocytopenia and thrombosis (VITT). The invention has use in both the medical and veterinary industries.

A method of treating a synucleinopathy with a peptide

TABLE-US-00001 (C)DQPVLPD (SEQ ID NO: 59), (C)DMPVLPD (SEQ ID NO: 60), (C)DSPVLPD (SEQ ID NO: 61), (C)DQPVLPDN (SEQ ID NO: 64), (C)DMPVLPDN (SEQ ID NO: 65), (C)DSPVLPDN (SEQ ID NO: 66), (C)HDRPVTPD (SEQ ID NO: 70), (C)DRPVTPD (SEQ ID NO: 71), (C)DVPVLPD (SEQ ID NO: 72), (C)DTPVYPD (SEQ ID NO: 73), (C)DTPVIPD (SEQ ID NO: 74), (C)HDRPVTPDN (SEQ ID NO: 75), (C)DRPVTPDN (SEQ ID NO: 76), (C)DVPVLPDN (SEQ ID NO: 78), (C)DTPVYPDN (SEQ ID NO: 79), (C)DQPVLPDG (SEQ ID NO: 81), (C)DMPVLPDG (SEQ ID NO: 82), (C)DSPVLPDG (SEQ ID NO: 83), (C)DHPVHPDS (SEQ ID NO: 86), (C)DMPVSPDR (SEQ ID NO: 87), (C)DRPVYPDI (SEQ ID NO: 90), (C)DHPVTPDR (SEQ ID NO: 91), (C)DTPVLPDS (SEQ ID NO: 93), (C)DMPVTPDT (SEQ ID NO: 94), (C)DAPVTPDT (SEQ ID NO: 95), (C)DSPWPDN (SEQ ID NO: 96), (C)DLPVTPDR (SEQ ID NO: 97), (C)DSPVHPDT (SEQ ID NO: 98), (C)DAPVRPDS (SEQ ID NO: 99), (C)DMPVWPDG (SEQ ID NO: 100), (C)DRPVQPDR (SEQ ID NO: 102), (C)YDRPVQPDR (SEQ ID NO: 103), (C)DMPVDADN (SEQ ID NO: 105), DQPVLPD(C) (SEQ ID NO: 106), and DMPVLPD(C) (SEQ ID NO: 107.

The invention provides methods and compositions for treating cancer and for enhancing immune function in an individual having cancer. The methods comprise administering a PD-1 axis binding antagonist and a taxane.

Provided herein are methods and compositions for treating solid tumor cancers.

This invention provides a composition of matter comprising a plurality of cocaine-succinyl-BSA, wherein the average ratio of cocaine-succinyl moieties to BSA is at least 7.0. This invention also provides a composition of matter comprising a plurality of nicotine-5-succinyl-BSA, wherein the average ratio of nicotine-5-succinyl moieties to BSA is at least 7.0. This invention further provides a composition of matter comprising a plurality of methamphetamine-5-succinyl-BSA, wherein the average ratio of methamphetamine-5-succinyl moieties to BSA is at least 7.0. This invention still further provides related pharmaceutical compositions, therapeutic methods, prophylactic methods, synthetic methods, and articles of manufacture.

A method for reversing immune suppression or immune exhaustion or for treating a disease associated with immune suppression includes: administering a composition to a subject in need of such treatments, wherein the composition contains a CD11b modulator that binds specifically to CD11b on a cell to inhibit PD-L1 expression. The CD11b modulator is an antibody or an antigen-binding portion thereof, or a compound as described.

The present invention relates to methods of treating pancreatic cancer with particular dosage regimes of antibodies that bind colony stimulating factor 1 receptor (CSF1R) (e.g. cabiralizumab) in combination with antibodies that bind programmed cell death 1 (PD-1) (e.g. nivolumab).

The present disclosure relates to an immunologically active peptide-biliverdin conjugate (I), a preparation method therefor and an application thereof in cancer diagnosis, and/or tumor immunotherapy, and/or tumor “photothermal immunotherapy” (tumor photothermal therapy combined with immunotherapy). The conjugate to which the present disclosure relates not only may stimulate an organism to generate a tumor-immune effect, but also may relieve and/or eliminate tumor inflammation, remodel a tumor inflammatory microenvironment and achieve photothermal cancer immunodiagnosis and immunotherapy. The conjugate to which the present disclosure relates has high biocompatibility, good stability and an extended half-life. The conjugate is prepared from an immunologically active peptide and biliverdin by means of chemical synthesis. A peptide end of the conjugate exercises the function of immunoregulation, and a pigment end thereof exercises functions such as tumor imaging diagnosis, tumor photo-thermal ablation, immune inflammatory microenvironment regulation and the like. The conjugate may significantly enhance the antitumor effect and effectively inhibit tumor metastasis and recurrence.