Prostate Cancer Vaccines Generated with the Disruptive RNActive® Technology Follow the Path Paved by Sipuleucel-T and Prostvac-VF

Somewhat surprisingly, the first active cancer immunotherapy was approved with sipuleucel-T, an autologous cell therapy, in castrate-resistant prostate carcinoma rather than in melanoma, the test disease for many immunotherapies in the past. Sipuleucel-T is followed suit by other vaccines against prostate carcinoma that are now on advanced clinical development paths. Prostvac-VF is a viral vector vaccine using a heterologous prime–boost regimen to target PSA that has delivered promising phase IIb results. CV9103 is the first example in clinical testing of a vaccine engineered with the RNActive® technology. This technology uses a sequence modified mRNA molecule to ensure enhanced protein (antigen) expression and achieves good immune stimulation at the time by activation of TLR7. The nucleotide basis of CV9103 allowed inclusion of four different prostate-associated antigens in the vaccine. Safety and good immunogenicity of this novel approach were successfully demonstrated in a phase I/IIa study, and a further development of it is now in clinical phase IIb, proof-of-concept testing. These active immunotherapies can be combined successfully with other immunotherapies such as checkpoint inhibitors and may become pillars of anticancer immunotherapies.