Antibody-drug conjugates comprising anti-TM4SF1 antibodies and methods of using the same

An antibody-drug conjugate comprising (1) an anti-transmembrane 4 L six family member 1 (TM4SF1) antibody or an antigen binding fragment thereof conjugated to (2) a therapeutic molecule via a linker, wherein the anti-TMA4SF1 antibody or the antigen binding fragment thereof comprises a human IgG1 Fc region comprising (1) a cysteine residue at position N297, or (2) a cysteine residue at position N297 and one or more mutations selected from the group consisting of M252Y, S254T, and T256E;

• as numbered by the EU index as set forth in Kabat, wherein the linker comprises (1) acetamide and (2) a spacer of C6 alkylene, wherein the therapeutic molecule is conjugated to the cysteine at position 297, and wherein the anti-TM4SF1 antibody or the antigen binding fragment thereof comprises:
• (a) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 6, 7, and 8, respectively;
• and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 12, 13, and 14, respectively;
• (b) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 18, 19, and 20, respectively;
• and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 24, 25, and 26, respectively;
• (c) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 30, 31, and 32, respectively;
• and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 36, 37, and 38, respectively;
• (d) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 42, 43, and 44, respectively;
• and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 48, 49, and 50, respectively;
• (e) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 54, 55, and 56, respectively;
• and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 60, 61, and 62, respectively;
• (f) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 66, 67, and 68, respectively;
• and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 72, 73, and 74, respectively;
• (g) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 78, 79, and 80, respectively;
• and a light chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 84, 85, and 86, respectively;
• (h) a heavy chain comprising a CDR1, CDR2, and CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 94, 95, and 96, respectively;
• and a light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NOs:
• 107 or 108, a CDR2 comprising the amino acid sequence of SEQ ID NO:
• 109, a CDR3 comprising the amino acid sequence of SEQ ID NOs:
• 110 or 111;
• or
• (i) a heavy chain comprising a CDR1 domain comprising the amino acid sequence of SEQ ID NO:
• 115, a CDR2 domain comprising the amino acid sequence of SEQ ID NOs:
• 116 or 117, a CDR3 domain comprising the amino acid sequence of SEQ ID NOs:
• 118, 119, 120, or 121;
• and a light chain comprising a CDR1 domain comprising the amino acid sequence of SEQ ID NOs:
• 124, 125, 126, or 127, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:
• 128, a CDR3 domain comprising the amino acid sequence of SEQ ID NO:
• 129.