An isolated monoclonal antibody, or an antigen-binding portion thereof, binding to Claudin 18.2, comprising: a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 2, 4, and 8, respectively, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 11, 13 and 16, respectively, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs: 18 and 51, respectively; SEQ ID NOs: 22 and 55, respectively; or SEQ ID NOs: 28 and 57, respectively; a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 2, 4, and 9, respectively, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 10, 14 and 16, respectively, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs: 19 and 52, respectively; SEQ ID NOs: 29 and 58, respectively; SEQ ID NOs: 32 and 58, respectively; or SEQ ID NOs: 35 and 60, respectively; a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 2, 5, and 9, respectively, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 12, 13 and 16, respectively, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs: 20 and 53, respectively; SEQ ID NOs: 36 and 61, respectively; SEQ ID NOs: 42 and 62, respectively; or SEQ ID NOs: 42 and 63, respectively; or a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 3, 6, and 8, respectively, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 10, 15 and 16, respectively, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs: 21 and 54, respectively; SEQ ID NOs: 43 and 64, respectively; or SEQ ID NOs: 49 and 66, respectively. a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 2, 4, and 8, respectively, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 11, 13 and 16, respectively, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs: 18 and 51, respectively; SEQ ID NOs: 22 and 55, respectively; or SEQ ID NOs: 28 and 57, respectively; a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 2, 4, and 9, respectively, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 10, 14 and 16, respectively, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs: 19 and 52, respectively; SEQ ID NOs: 29 and 58, respectively; SEQ ID NOs: 32 and 58, respectively; or SEQ ID NOs: 35 and 60, respectively; a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 2, 5, and 9, respectively, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 12, 13 and 16, respectively, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs: 20 and 53, respectively; SEQ ID NOs: 36 and 61, respectively; SEQ ID NOs: 42 and 62, respectively; or SEQ ID NOs: 42 and 63, respectively; or a heavy chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 3, 6, and 8, respectively, and a light chain variable region comprising a CDR1, a CDR2, and a CDR3 comprising the amino acid sequences of SEQ ID NOs: 10, 15 and 16, respectively, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs: 21 and 54, respectively; SEQ ID NOs: 43 and 64, respectively; or SEQ ID NOs: 49 and 66, respectively.