Abstract: Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGF? and/or LTBP3-TGF?. The application also provides methods of use of these inhibitors for, for example, inhibiting TGF? activation, and treating subjects suffering from TGF?-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGF? inhibitor for a subject in need thereof are also provided.

Abstract: The invention provides method of treating fibrosis, comprising the steps of (a) selecting a TGF? inhibitor for the treatment of fibrosis, (1) wherein the TGF? inhibitor (A) specifically binds a LTBP1-proTGF? complex; (B) does not bind a human GARP-proTGF? complex; (C) does not bind a human LRRC33-proTGFp complex; and (D) does not bind mature TGF?1, mature TGF?2 or mature TGF?3; and (2) wherein the TGF? inhibitor is selected using an assay to measure the amount of a marker, wherein the amount of the marker is indicative of the treatment of fibrosis, with the proviso that the marker is not pSmad2; and (b) providing the selected TGF? inhibitor for administration to a subject in need of treatment for fibrosis. These selected TGF? inhibitor are isoform-specific, context-selective inhibitors of TGF?1 that selectively target matrix-associated TGF?1 activation but not immune cell-associated TGF?1 activation.

Abstract: The present disclosure provides TGF? inhibitor therapy for treating immunosuppressive conditions, cancer, and fibrosis, either as a monotherapy or combination/adjunct therapy. Selection of suitable therapy and patients who are likely to benefit from such therapy are also disclosed, as well as methods of treating cancer and fibrosis and methods of predicting and monitoring therapeutic response. Related compositions, methods and therapeutic use are also disclosed.

Abstract: Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGF? and/or LTBP3-TGF?. The application also provides methods of use of these inhibitors for, for example, inhibiting TGF? activation, and treating subjects suffering from TGF?-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGF? inhibitor for a subject in need thereof are also provided.

Abstract: Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGF? and/or LTBP3-TGF?. The application also provides methods of use of these inhibitors for, for example, inhibiting TGF? activation, and treating subjects suffering from TGF?-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGF? inhibitor for a subject in need thereof are also provided.

Abstract: Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGF? and/or LTBP3-TGF?. The application also provides methods of use of these inhibitors for, for example, inhibiting TGF? activation, and treating subjects suffering from TGF?-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGF? inhibitor for a subject in need thereof are also provided.

Abstract: Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGF? and/or LTBP3-TGF?. The application also provides methods of use of these inhibitors for, for example, inhibiting TGF? activation, and treating subjects suffering from TGF?-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGF? inhibitor for a subject in need thereof are also provided.

Abstract: Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGF? and/or LTBP3-TGF?. The application also provides methods of use of these inhibitors for, for example, inhibiting TGF? activation, and treating subjects suffering from TGF?-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGF? inhibitor for a subject in need thereof are also provided.