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folinic acid + fluorouracil + oxaliplatin + PD-1 monoclonal antibody

Development stage
Preclinical
Lead developer
Agenus
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous
01

Overview

The drug combination "folinic acid + fluorouracil + oxaliplatin + PD-1 monoclonal antibody" represents an advanced therapeutic regimen that combines traditional chemotherapy agents with immunotherapy for cancer treatment. ## Description This combination therapy consists of three chemotherapeutic agents (folinic acid, fluorouracil, and oxaliplatin) known collectively as FOLFOX, plus a PD-1 monoclonal antibody immunotherapy agent. The FOLFOX component has been a standard treatment for colorectal cancer for decades[1][7]. The mechanism involves multiple complementary actions: - **Oxaliplatin**: A third-generation platinum analog that forms reactive platinum complexes which inhibit DNA synthesis by creating inter-strand and intra-strand cross-linking of DNA molecules, disrupting DNA replication and transcription[5]. Its bulky DACH side groups inhibit DNA base excision by mismatching repair enzymes, which is particularly effective in colorectal cancer where these repair enzymes are highly active[8]. - **Fluorouracil (5-FU)**: A pyrimidine analog that interferes with DNA and RNA synthesis. Its activity is enhanced by folinic acid. - **Folinic acid (leucovorin)**: Not cytotoxic itself but enhances the efficacy of 5-fluorouracil by stabilizing the binding of 5-FU to its target enzyme, thymidylate synthase. - **PD-1 monoclonal antibody**: Blocks the interaction between PD-1 (programmed cell death protein 1) and its ligands, preventing cancer cells from evading immune surveillance and enhancing T-cell anti-tumor activity. The addition of a PD-1 inhibitor to FOLFOX represents an evolution in treatment strategy, combining cytotoxic effects with immunogenic cell death induction, potentially creating synergistic chemo-immunotherapeutic effects[7].

Other names
FOLFOX + PD-1 inhibitorFOLFOX + immune checkpoint inhibitor
02

Targets

PDCD1 (Programmed cell death protein 1 receptor)DNATS (Thymidylate synthase)

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