The main effect of<unk>  is due to its metabolite phosphoramide mustard. This metabolite is only formed in cells that have low levels of ALDH. Phosphoramide mustard forms DNA crosslinks both between and within DNA strands at guanine N-7 positions (known as interstrand and intrastrand crosslinkages, respectively). This is irreversible and leads to cell apoptosis.<unk>  has relatively little typical chemotherapy toxicity as ALDHs are present in relatively large concentrations in bone marrow stem cells, liver and intestinal epithelium. ALDHs protect these actively proliferating tissues against toxic effects of phosphoramide mustard and acrolein by converting aldophosphamide to carboxycyclophosphamide that does not give rise to the toxic metabolites phosphoramide mustard and acrolein. This is because carboxycyclophosphamide cannot undergo β-elimination (the carboxylate acts as an electron-donating group, nullifying the potential for transformation), preventing nitrogen mustard activation and subsequent alkylation.<unk>  induces beneficial immunomodulatory effects in adaptive immunotherapy. Suggested mechanisms include: # Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts # Induction of T cell growth factors, such as type I IFNs, and/or # Enhanced grafting of adoptively transferred, tumor-reactive effector T cells by the creation of an immunologic space niche. Thus,<unk>  preconditioning of recipient hosts (for donor T cells) has been used to enhance immunity in naïve hosts, and to enhance adoptive T cell immunotherapy regimens, as well as active vaccination strategies, inducing objective antitumor immunity.
Cyclophosphamide
Ifosfamide
Vincristine
Lenalidomide
Mitoxantrone
Cytarabine
Cladribine
Phototrexate