Abstract: The invention provides macromolecule-supported compounds of Formula I comprising a macromolecule linked by conjugation to one or more 8-sulfonyl-2-aminobenzazepine derivatives. The invention also provides 8-sulfonyl-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the macromolecule-supported compounds through a linker or linking moiety. The invention further provides methods of treating cancer with the macromolecule-supported compounds.

Abstract: The invention provides immunoconjugates of Formula. (I) comprising an antibody linked by conjugation to one or more 8-sulfonyl-2-aminobenzazepine derivatives. The invention also provides 8-sulfonyl-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more STING agonist moieties. The invention also provides STING agonist-linker intermediate compounds comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates comprising a cysteine-mutant antibody covalently attached to one or more TLR agonist moieties by a linker. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates of Formula (I): Ab-[L-D]p, comprising an antibody linked by conjugation to one or more STING agonist moieties. The invention also provides STING agonist-linker intermediate compounds comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: STING pathway agonism has emerged as a potential therapeutic mechanism to stimulate an innate anti-tumor immune response. While in principle systemic administration of a STING agonist would have many therapeutic benefits, including the delivery of STING to all tumor lesions, such an approach may be limited by toxicity. Antibody-drug conjugates (ADCs) constitute a proven therapeutic modality that is ideally suited to enable systemic administration without associated toxicity concerns via a targeted delivery strategy. Herein, we demonstrate that systemically administered STING agonist ADCs have greater anti-tumor activity as well as greatly improved tolerability compared to an intravenously (IV) administered, unconjugated (free) agonist. We generated novel STING agonist ADCs by leveraging our Immunosynthen platform, in which the chemical scaffold for bioconjugation is optimized for the STING agonist, resulting in an ADC that has desirable physicochemical and drug-like properties.

Abstract: The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more 2-amino-4-carboxamide-benzazepine derivatives. The invention also provides 2-amino-4-carboxamide-benzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates of Formula I comprising an anti-CEA antibody linked by conjugation to one or more 8-phenyl-2-aminobenzazepine derivatives. The invention also provides 8-phenyl-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more 2-amino-4-carboxamide-benzazepine derivatives. The invention also provides 2-amino-4-carboxamide-benzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates of Formula I comprising an anti-HER2 antibody linked by conjugation to one or more 8-Het-2-aminobenzazepine derivatives. The invention also provides 8-Het-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates of Formula I comprising an anti-HER2 antibody linked by conjugation to one or more 8-phenyl-2-aminobenzazepine derivatives. The invention also provides 8-phenyl-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates of Formula I comprising an anti-PD-L1 antibody linked by conjugation to one or more 8-Cyc-2-aminobenzazepine derivatives. The invention also provides 8-Cyc-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention relates to dendritic cell-associated C-type lectin 2 (Dectin-2) binding agents, nucleic acids comprising the inventive binding agents, vectors and cells comprising the inventive nucleic acids, and compositions thereof. The invention also relates to methods of providing the inventive binding agents, methods for treating a disease, disorder, or condition in a mammal, and methods of stimulating an antigen presenting cell.

Abstract: The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more thienoazepine derivatives. The invention also provides thienoazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides immunoconjugates of Formula I comprising a cell-binding agent linked by conjugation to one or more immunostimulatory moieties where the linker is a substrate for elastase. The invention also provides immunostimulant intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention relates to dendritic cell-associated C-type lectin 2 (Dectin-2) binding agents, nucleic acids comprising the inventive binding agents, vectors and cells comprising the inventive nucleic acids, and compositions thereof. The invention also relates to methods of providing the inventive binding agents, methods for treating a disease, disorder, or condition in a mammal, and methods of stimulating an antigen presenting cell.

Abstract: The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more pyrazoloazepine derivatives. The invention also provides pyrazoloazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Abstract: The invention provides macromolecule-supported compounds of Formula I comprising a macromolecular support linked by conjugation to one or more thienoazepine derivatives. The invention also provides thienoazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the macromolecule-supported compounds through a linker or linking moiety. The invention further provides methods of treating cancer with the macromolecule-supported compounds.

Abstract: The invention provides methods for treating cancer in a subject comprising administering an immunoconjugate of formula: Ab-[TA]r or a pharmaceutically acceptable salt thereof, wherein “Ab” is an antibody construct that has an antigen binding domain that binds human epidermal growth factor receptor type 2 (HER2) and “TA” is a therapeutic agent of formula: wherein n is from about 2 to about 25 and r is an average therapeutic agent to antibody ratio from 1 to 10, to a subject having cancer.

Abstract: The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more thienoazepine derivatives. The invention also provides thienoazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.