Chemotherapy

Class

Chemotherapy (lymphodepleting conditioning regimen: fludarabine, a purine-analog antimetabolite, plus cyclophosphamide, an alkylating agent)

Pathway

Lymphodepletion prior to adoptive cell therapy infusion

Notes

original target text: Chemotherapy (lymphodepleting conditioning regimen: fludarabine, a purine-analog antimetabolite, plus cyclophosphamide, an alkylating agent)

This mechanism describes a two-drug chemotherapy regimen given not to treat a tumor directly, but to prepare a patient's immune system to receive an infusion of engineered or expanded immune cells, such as CAR-T cells. Fludarabine is a purine-analog antimetabolite: it is incorporated into DNA and blocks the enzymes needed for DNA synthesis and repair, killing dividing lymphocytes. Cyclophosphamide is an alkylating agent that chemically cross-links DNA strands, causing breaks that are lethal to proliferating cells, including lymphocytes. Together they produce transient but pronounced lymphodepletion, a marked reduction in the patient's own circulating T cells, B cells, and natural killer cells. The biological rationale is twofold: removing competing and regulatory immune cells that would otherwise limit expansion of the infused therapeutic cells, and creating physiological space and cytokine signals that favor their engraftment and proliferation. This conditioning strategy is broadly relevant across adoptive cell therapies for hematologic and solid cancers, where the persistence and expansion of transferred cells strongly influences clinical benefit. It is not intended as an independent anticancer treatment in this context, though both agents also have direct cytotoxic activity against malignant lymphocytes.