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LM-302 + gemcitabine is a combination therapy consisting of LM-302, an antibody-drug conjugate (ADC) targeting claudin 18.2 (CLDN18.2), and gemcitabine, a nucleoside analog chemotherapy agent. LM-302 is composed of a recombinant humanized anti-CLDN18.2 IgG1 monoclonal antibody linked by a cleavable VC-PAB linker to the payload monomethyl auristatin E (MMAE), a potent tubulin polymerization inhibitor. LM-302 specifically targets CLDN18.2-expressing tumor cells, leading to internalization and subsequent release of MMAE, which disrupts microtubule dynamics, arrests cell division, and induces apoptosis. Gemcitabine inhibits DNA synthesis by incorporation into DNA and by inhibiting ribonucleotide reductase, resulting in cytotoxicity primarily during the S-phase of the cell cycle. This combination is being investigated for enhanced anti-tumor activity in CLDN18.2-positive solid tumors, particularly gastrointestinal cancers, pancreatic cancer, gastric and gastroesophageal junction cancers.
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