Disclosed are surprising new methods and kits for treating patients, particularly cancer patients, using bavituximab in combination therapies with immuno-oncology (IO) agents such as checkpoint inhibitor antibodies. The methods and kits are based on the surprising finding that human patients treated with bavituximab and checkpoint inhibitor antibodies have a statistically significant prolonged survival in controlled studies.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

Provided is a novel method for preparing a long-acting drug conjugate and a long-acting drug conjugate prepared using the method.

This invention, inter alia, relates to CD19 binding agents and methods of using such CD19 binding agents for treating disease.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

Conjugates comprising a coagulating agent conjugated to an antibody, where the antibody specifically binds an extracellular domain epitope of a mammalian PLVAP protein, and methods of using such conjugates, including methods of treating HCC by administering the conjugates or compositions thereof, such as pharmaceutical compositions.

Aspects of the disclosure relate to antibodies that bind to transferrin receptor (e.g., transferrin receptor 1) and complexes comprising the antibody covalently linked to a molecular payload. Methods of using the antibodies are also provided.

Infection with obligatory intracellular bacteria is difficult to treat as intracellular targets and delivery methods of therapeutics are not well-known. Ehrlichia translocated factor-1 (Etf-1), a type IV secretion system (T4SS) effector, is a primary virulence factor for an obligatory intracellular bacterium, Ehrlichia chaffeensis. Disclosed herein are Etf-1-specific nanobodies (Nbs) that block Etf-1 functions and Ehrlichia infection. Also disclosed is a method for treating human monocytic ehrlichiosis (HME) in a subject with the disclosed nanobodies.

Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises

##STR00001##

wherein R′ is —H or —CH.sub.3, wherein R is —NR.sup.1R.sup.2, wherein R.sup.1 and R.sup.2 are alkyl groups, wherein R.sup.1 and R.sup.2 are the same or different, wherein R.sup.1 and R.sup.2 together have from 5 to 16 carbons, wherein R.sup.1 and R.sup.2 may optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.

CD47+ disease cells such as cancer cells are treated using a combination of CD47 blockade drug and a proteasome inhibitor. The anti-cancer effect of one drug enhances the 5 anti-cancer effect of the other. Specific combinations include SIRPαFc as CD47 blockade drug, and one of bortezomib, ixazomib and carfilzomib as proteasome inhibitor. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.