Methods of using anti-lap antibodies
AssigneeTilos Therapeutics, Inc.
InventorsBarbara S. Fox, Randall Burton, Stavros Kopsiaftis, Xiufeng Song, Patricia Rao, Kenneth J. Simon, Jessie M. English
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Abstract
Provided herein are antibodies which bind to latency-associated peptide (LAP) of TGF-β1 and are characterized by particular functional features, such as binding specifically to LAP-TGFβ1 on cells but not to LAP-TGFβ1 in extracellular matrix, as well as compositions including the same. Also provided are uses of these antibodies in therapeutic applications, such as in the treatment of cancer, and diagnostic applications.
Claims14
A method of selectively inhibiting TGFβ1 activation on immunosuppressive cells in a subject having cancer comprising:
- (a) contacting a plurality of anti-LAP antibodies with recombinant:
- (i) human LAP-TGFβ1 (SEQ ID NO:
- 2) in the absence of an anchor protein selected from the group consisting of:
- GARP and LRRC33;
- (ii) human LAP-TGFβ1 complexed with the anchor protein;
- and
- (iii) human LAP-TGFβ1 complexed with LTBP1, LTBP3 and/or LTBP4;
- (b) determining TGFβ1 inhibition of (a)(i)-a(ii) by the plurality of anti-LAP antibodies using an enzyme-linked immunosorbent assay (ELISA), respectively;
- (c) determining binding of (a)(iii) by the plurality of anti-LAP antibodies;
- (d) selecting an antibody that:
- (i) inhibits TGFβ1 in step (b) for (a)(i) and (a)(ii);
- and
- (ii) does not bind (a)(iii) in step (b);
- and
- (e) administering an amount of the antibody selected in (d) to the subject such that TGFβ1 is selectively inactivated on the immunosuppressive cells in the subject,
- wherein the plurality of anti-LAP antibodies comprises an antibody that comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:
- 22 and light chain variable region comprising the amino acid sequence of SEQ ID NO:
- 23, and
- wherein step (d) further comprises selecting the antibody that (i) inhibits TGFβ1 in step (b) for (a)(i) and (a)(ii) to an equal or greater degree than the antibody that comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:
- 22 and light chain variable region comprising the amino acid sequence of SEQ ID NO:
- 23.
Dependencies are inferred from the claim text.