Disclosed herein are methods for high-throughput screening of a functional antibody fragment for an immunoconjugate that targets a protein antigen. The method combines a phage-displayed synthetic antibody library and high-throughput cytotoxicity screening of non-covalently assembled immunotoxins or cytotoxic drug to identify highly functional synthetic antibody fragments for delivering toxin payloads.

Disclosed herein are therapeutic constructs including a delivery particle, at least one mitotic kinase inhibitor, and at least one immune checkpoint inhibitor. Also disclosed are therapeutic constructs including a mitotic kinase inhibitor, an immune checkpoint inhibitor, and a chemical linker. These therapeutic constructs cause cancer death by both therapeutic and immune effects and promote targeted delivery of more therapeutics to the surviving cancer cells in a positive feed-back loop. They enhance therapeutic index of free drugs and can be used intratumorally or systemically. This strategy can treat broad cancer types and is particular useful for cancer without obvious receptors for cancer-targeted delivery of otherwise toxic therapeutics.

The present invention generally relates to T cell activating bispecific antigen binding molecules, PD-1 axis binding antagonists, and in particular to combination therapies employing such T cell activating bispecific antigen binding molecules and PD-1 axis binding antagonists, and their use of these combination therapies for the treatment of cancer.

Normal or genetically modified cell(s) having magnetic nanoparticle(s) bound (affixed) to their surfaces and methods of delivery to target tissues, e.g. For treatment of disease and/or injury.

The present invention relates to compositions and methods associated with antibody-bacterial effector translocase protein conjugates. Some aspects of the present invention relate to preventing or treating diseases using the antibody-protective antigen conjugates. Further aspects of the present invention relate to methods of chemically conjugating and synthesizing the antibody-bacterial effector translocase protein conjugates.

The present disclosure provides a targeted delivery platform for delivery of a therapeutic molecule to a target cell. The targeted delivery platform includes a complex that includes the therapeutic molecule, a polyalkylene glycol polymer and a targeting protein. Also provided herein are methods of making the complex and methods of using the complex to deliver the therapeutic molecule to a target cell to achieve treatment of a disease.

The present disclosure is related to compositions of antibodies and immunoconjugates that potentially lack T-cell epitopes and elicit reduced immune response. The antibody may be an antibody fragment, such as Fab, Fab′, F(ab′)2, scFv, dsFv, ds-scFv, dimers, minibodies, diabodies, bispecific antibody fragments, multimers, and any combination thereof. In a further embodiment, the antibody may bind to an antigen epithelial cell adhesion molecule (EpCAM). In another embodiment, an immunoconjugate may comprise an antibody attached to an effector molecule, wherein the effector molecule may be a radioisotope, an antineoplastic agent, an immunomodulator, a biological response modifier, lectin, a toxin, a chromophore, a fluorophore, a chemiluminescent compound, an enzyme, a metal ion, and any combination thereof.

Described is a conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. Also described are a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.

The drug component of an antibody-drug conjugate having a structure according to formula (II), where Ab, m, n, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are as defined in the application, exhibits unexpectedly improved stability.

##STR00001##

An antibody-drug conjugate having a structure represented by formula (I)

##STR00001##

wherein m is 1, 2, 3, or 4 and Ab is an anti-glypican-3 antibody having heavy and light chain CDRs as disclosed herein.