Patients with acute promyelocytic leukaemia (APL) are typically treated with all-trans retinoic acid (ATRA), but this drug provides only short-term remission, so additional strategies are needed. In the November issue of Nature Medicine, Rose Ann Padua and colleagues describe a vaccine that prolongs survival when administered in combination with ATRA in a mouse model of this cancer.

APL is associated with a chromosome translocation that causes production of the PML–RARα fusion protein, which disrupts differentiation of the myeloid-cell lineage. A transgenic mouse model of this disease has been developed and can be used to test new treatment strategies. Because PML–RARα is not normally expressed by cells, it represents a good target for immunotherapy.

Padua et al. vaccinated mice with DNA that encoded PML–RARα fused to the FrC gene, which encodes the highly immunogenic tetanus toxin fragment C. These mice mounted a strong immune response against PML–RARα, as shown by production of antibodies and a T-cell response against the oncoprotein, as well as increased interferon-γ production. The addition of the FrC gene to the vector markedly enhanced the immune response against PML–RARα. Furthermore, 56% of leukaemic mice that received the PML–RARA–FrC vaccine had significantly extended survival, compared with mice injected with vector alone.

But how does this vaccine compare with ATRA treatment? Vaccine-treated mice lived almost as long as ATRA-treated mice. When the two therapeutics were combined, however, mice could live over 40% longer than with either treatment alone. The authors suggest that by boosting the immune response against tumour antigens, DNA vaccination can provide added value in the control of residual disease after ATRA therapy in humans.