Fludarabine (Fludara, Oforta)

Description

Fludarabine is a purine nucleoside analog chemotherapy agent used as a lymphodepleting agent in adoptive T-cell therapy protocols for colorectal cancer. In CRC treatment, it serves as a preparative conditioning regimen to deplete host lymphocytes before infusion of tumor-infiltrating lymphocytes (TILs) or genetically modified T-cells targeting KRAS mutations. This lymphodepletion creates immunologic space and reduces regulatory T-cells, enhancing the expansion and anti-tumor activity of subsequently infused therapeutic T-cells. Fludarabine is specifically utilized in advanced CRC patients with MSI-H tumors or KRAS mutations as part of cellular immunotherapy approaches.

Mechanism of Action

Fludarabine is metabolized intracellularly to fludarabine triphosphate, which inhibits DNA polymerase and ribonucleotide reductase, leading to DNA synthesis inhibition and cell death. The drug preferentially targets lymphocytes due to their high levels of deoxycytidine kinase and low levels of 5'-nucleotidase, resulting in selective lymphoid depletion. This lymphodepletion eliminates competing T-cells and immunosuppressive cells, creating favorable conditions for adoptively transferred therapeutic T-cells to expand and function effectively.

Molecular Targets

Side Effects

Not all side effects are listed. Side effects vary by individual. Always consult your oncologist.

Clinical Trials