TGFbeta1-binding immunoglobulins and use thereof

A method for making a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds specifically to transforming growth factor beta 1 (TGFβ1), the method comprising:

• (a) providing a plurality of anti-TGFβ1 candidate antibodies or antigen-binding fragments thereof;
• (b) performing a binding assay with each of the candidate anti-TGFβ1 antibodies or antigen-binding fragments thereof to detect:
• (i) isoform-specific binding to a complex comprising TGFβ1 and not to a complex comprising TGFβ2 or TGFβ3;
• and
• (ii) binding to human or murine proTGFβ1 comprising a cysteine to serine mutation at position 4 (proTGFβ1 C4S);
• thereby identifying one or more candidate TGFβ1-specific antibodies or antigen-binding fragments thereof capable of (b)(i) and (ii);
• (c) performing a cell-based assay and tumor growth inhibition (TGI) analysis with each of the one or more candidate TGFβ1-specific antibodies or antigen-binding fragments thereof identified in step (b) to detect:
• (i) inhibition of protease-dependent release of human or murine TGFβ1 from the proTGFβ1 C4S;
• and
• (ii) inhibition of tumor growth when used in combination with a checkpoint inhibitor in a murine tumor model;
• thereby identifying one or more TGFβ1-specific antibodies or antigen-binding fragments thereof capable of (c)(i) and (ii);
• and
• (d) formulating the TGFβ1-specific antibody or antigen-binding fragment thereof identified in step (c) into a pharmaceutical composition comprising one or more pharmaceutically acceptable excipients.