The present application relates to a composition comprising (a) at least one immune checkpoint inhibitor and (b) at least one conjugate, wherein said conjugate is comprising (i) a target binding moiety, (ii) at least one amatoxin, and (iii) optionally at least one linker connecting said target binding moiety with said at least one amatoxin. The present application further relates to said composition for use in treating a patient having a cancer, and to a pharmaceutical formulation comprising said composition and additional excipients, as well as to methods of producing and using said composition.

Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO.sub.2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.

Among the various aspects of the present disclosure is the provision of conditioning agents for use in allogeneic hematopoietic stem cell transplantation. An aspect of the present disclosure provides for a method of treating a subject or inhibiting alloreactivity in the host-versus-graft direction comprising administering a combination of conditioning agents comprising an anti-body-drug conjugate (ADC) and a JAK1/JAK2 inhibitor for use in allogeneic hematopoietic stem cell transplantation in an amount sufficient to permit engraftment of allogeneic bone marrow. In some embodiments, the JAK inhibitor is selected from baricitinib. In some embodiments, the method comprises administering a cancer therapeutic.

The invention provides methods of depleting CD5+ cells in human patients undergoing chimeric antigen receptor (CAR) immunotherapy in order to promote acceptance of CAR expressing immune cells. Anti-CD5 antibody drug conjugates (ADCs) are administered as a conditioning regimen to a human patient receiving autologous or allogeneic CAR expressing immune cells such that the CAR expressing immune cells are accepted by the human patient. Compositions and methods of the invention can be used in combination with CAR therapy to treat a variety of pathologies, including autoimmune diseases and cancer.

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

The present invention pertains to treatment regimens to increase the therapeutic index of antibody-drug conjugates in particular antibody-drug conjuagtes comprising amatoxins. The present invention furthermore pertains to amatoxin-based antibody-drug conjuagtes for use in said treatment regimens.

The invention relates generally to antibodies, activatable antibodies, multispecific antibodies, and multispecific activatable antibodies that specifically bind to at least CD3, as well as to methods of making and using these antibodies, activatable antibodies, multispecific antibodies, and/or multispecific activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications.

The present invention relates to a method for generating an antibody-payload conjugate by means of a microbial transglutaminase (MTG). The method comprises a step of conjugating a linker comprising or having the structure (shown in N—>C direction) Aax-(Sp.sub.1)-B.sub.1-(Sp.sub.2) via a primary amine in the N-terminal residue Aax to a glutamine (Gln) residue comprised in the heavy or light chain of an antibody, wherein Aax is an amino acid having the structure NH.sub.2—Y—COOH, wherein Y comprises a substituted or unsubstituted alkyl or heteroalkyl chain; (Sp.sub.1) is a chemical spacer or is absent; (Sp.sub.2) is a chemical spacer or is absent; and B.sub.1 is a linking moiety or a payload. Further the present invention relates to antibody-linker conjugates that have been generated with the method of the invention and uses thereof.

The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.

The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6′ of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6′ of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.