The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.

Provided is an anti-human transferrin receptor antibody or an analog thereof, wherein in the heavy chain variable region of the antibody, (a) CDR1 comprises the amino acid sequence set forth as SEQ ID NO: 62 or SEQ ID NO: 63, (b) CDR2 comprises the amino acid sequence set forth as SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 comprises the amino acid sequence set forth as SEQ ID NO: 15 or SEQ ID NO: 16, and an analogue thereof.

The present disclosure relates to composition and methodology for using the CD2 receptor to block viral replication, such as HIV-1 infection. In one embodiment, viral target cells such as blood CD4 T cells can be rendered resistant to HIV through stimulation of the CD2 receptor with either an antibody, a ligand, or a small molecule that binds to the CD2 receptor. Pre-stimulation of CD2 can be used to enhance the anti-HIV immunity and used to promote immune response from HIV infection or from an anti-HIV vaccine.

The invention relates to dosing regimens for antibody drug conjugates, as well as methods of administering said dosing regimens to patients suffering from or at risk of various diseases and conditions such as autoimmune diseases, cancers, and Graft versus Host Disease (GvHD), among others, by administration of an antibody drug conjugate (ADC), capable of binding an antigen expressed by a hematopoietic cell, such as a hematopoietic stem cell, an immune cell or a cancer cell.

The invention provides methods of depleting CD2+ cells in human patients undergoing chimeric antigen receptor (CAR) immunotherapy in order to promote acceptance of CAR expressing immune cells. Anti-CD2 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 present disclosure provides CD19 binding molecules that specifically bind to CD19, including monospecific, bispecific and trispecific binding molecules, conjugates comprising the CD19 binding molecules, and pharmaceutical compositions comprising the CD19 binding molecules and the conjugates. The disclosure further provides methods of using the C19 binding molecules to treat diseases and disorders associated with expression of CD19. The disclosure yet further provides recombinant host cells engineered to express the CD19 binding molecules and methods of producing the CD19 binding molecules by culturing the host cells under conditions in which the CD19 binding molecules are expressed.

Provided herein are methods of in-vitro primary T cell growth that enrich T cells in a blood sample, stimulate the T cells with anti-CD2, anti-CD3, and/or anti-CD28 and that expand the T cells with a cytokine. Also provided are methods of treating a tumor in a patient using the expanded T cells.

The invention relates to a composition which induces, in a host, a cytotoxic cell response directed against cells expressing an antigen, in particular tumour cells, and which comprises red blood cells containing said antigen. These red blood cells may be in the form of an immune complex with an immunoglobulin, in particular IgG, which recognizes an epitope at the surface of the red blood cells, and/or be heat-treated or chemically treated so as to promote phagocytosis of said red blood cells by dendritic cells. As a variant, the red blood cells may be xenogenic red blood cells. The invention also relates to a therapeutic especially anti-tumour vaccine containing such a composition.

Provided are CCT5-binding molecules, including anti-CCT5 antibodies and antigen- binding fragments thereof such as heavy chain variable (VH) regions and single-chain antibody fragments, and conjugates comprising the anti-CCT5 binding molecules such as immunoconjugates and antibody-drug conjugates, and chimeric receptors comprising the anti-CCT5 binding molecules such as chimeric antigen receptors (CARs). In some embodiments, the anti-CCT5 antibodies or antigen-binding fragments thereof specifically bind to CCT5. Also provided are genetically engineered cells expressing the CARs or CCT5-binding molecules and uses thereof such as in adoptive cell therapy.

Disclosed are extracellular vesicles comprising an engineered targeting protein for targeting the extracellular vesicles to target cells. The targeting protein is a fusion protein that includes (i) an affinity agent, such as a single-chain variable fragment of an antibody (scFv), which is expressed on the surface of the extracellular vesicles and (ii) a transmembrane domain, and may include additional domains. Exemplary extracellular vesicles may include but are not limited to exosomes or microvesicles.