Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

The invention relates to compounds of general structure (1): Q-(L.sup.1).sub.n-(L.sup.2).sub.o-(L.sup.3).sub.p-(L.sup.4).sub.q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L.sup.1, L.sup.2, L.sup.3 and L.sup.4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21): ##STR00001##
wherein R.sup.12═C.sub.1-3-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L.sup.4).sub.q by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L.sup.6)-Z-(L.sup.1).sub.n-(L.sup.2).sub.o-(L.sup.3).sub.p-(L.sup.4).sub.q-D].sub.xx (2), wherein Z is a connecting group that is formed in a click reaction, L.sup.6 is a linker that links Z to Pr and Pr is a (glyco)protein.

The present invention provides cell-targeting molecules which can deliver a CD8+ T-cell epitope cargo to the MHC class I presentation pathway of the cell. The cell-targeting molecules of the invention can be used to deliver virtually any CD8+ T-cell epitope from an extracellular space to the MHC class I pathway of a target cell, which may be a malignant cell and/or non-immune cell. The target cell can then display on a cell-surface the delivered CD8+ T-cell epitope complexed with MHC I molecule. The cell-targeting molecules of the invention have uses which include the targeted labeling and/or killing of specific cell-types within a mixture of cell-types, including within a chordate, as well as the stimulation of beneficial immune responses. The cell-targeting molecules of the invention have uses, e.g., in the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections.

The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

A compound includes cytotoxic agents such as microcystin and nodularin. More specifically, a modified microcystin and/or nodularin compound contains one or more modified substrates, wherein one or more modified substrates include an anchor group directly accessible or transformable for use in conjugation chemistry (incl. click chemistry), for the attachment of a targeting moiety. This compound is useful for cancer treatment.

The invention provides anti-TIM3 antibodies and methods of using the same.

Provided herein are engineered non-catalytic, non-toxic tetanus toxin variants and methods of using such engineered tetanus toxin variants as low dose, protective vaccines that are non-toxic and more potent than their respective chemically inactivated toxoids. In addition, provided herein are conjugate vaccine carriers comprising engineered tetanus toxin variants and methods of using such conjugate vaccines to elicit T-cell dependent immune memory responses which can target a broad spectrum of microbial pathogens as a single vaccine.

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.

The invention provides methods or compositions for enhancing the potency of a targeted cancer immunotherapy in a subject by using a superantigen in combination with a PD-1 inhibitor.

Embodiments disclosed herein relate to compositions and methods for inducing transplantation tolerance using immunomodulation agents. In certain embodiments compositions and methods disclosed herein, concern administering a composition including, but not limited to, anti-CD3 immunotoxin and administering a composition including, but not limited to, peripheral blood cells obtained from a donor of an organ, tissue or cells to be transplanted. In some embodiments, compositions and methods disclosed here can be used for modulating B- and/or T-cell-mediated immunity and/or rejection by reducing or eliminating anti-donor antibody production. Other embodiments concern modulating T-cell production in a subject preparing for, undergoing organ, tissue or cellular transplantation; or having or expected of developing GvHD for reducing the risk of, preventing or treating rejection or GvHD. In certain embodiments, combination compositions of anti-CD3 immunotoxin and peripheral blood cells from a donor are contemplated.