FLT3 ligand enhances efficacy of RNA Vaccines in cancer therapy

Vaccines work on the principle of promote the immune system to recognize an invader and attack it more quickly, before it can do any harm. Recently, self-replicating RNA vaccines have emerged as an effective and safe approach to induce antitumor immunity. Self-replicating RNA can replicate in a diverse range of cell types, allows the expression of the Ag of interest at high levels, and eventually causes lysis of transfected cells.

Dendritic cells (DCs) are considered to be essential for vaccine effects of intranodal RNA[1], while the expansion of DCs is known to be induced by FLT3 ligand in the peripheral lymphoid organs and FLT3 ligand induced DCs have an immature phenotype[2].

In the lastest study, Kreiter et al. evaluates the effects of FLT3 ligand and intranodal RNA vaccination in the cancer therapy. FLT3 ligand treatment expands DCs and NK cells in the mouse lymph node and spleen compared to controls. When treatment by intranodally injected RNA combined with FLT3 ligand as adjuvant, Th1 lymph node milieu is induced to a larger extent, which leads to functional activation of DCs and NK cells thus integrating all factors involved in an efficient immune response. In animals treated with the combination, FLT3 ligand improves antitumoral immunity mediated by intranodal RNA vaccination[3].

In summary, these results show that FLT3 ligand may be a potent adjuvant for RNA-based cancer vaccine. Future researches should focus on the effects of RNA on TLR signaling pathways and clinical trials.

[1]. Cell 1993;75:1157-67.
[2]. Blood 2002;99:1676-82.
[3]. Cancer Res 2011; DOI:10.1158/0008-5472.CAN-11-0291.