The present invention generally relates to a personalized cancer vaccine comprising a recombinant poxvirus encoding one or more neopeptide(s) or a composition comprising such a recombinant poxvirus and a pharmaceutically acceptable vehicle as well as the use of the personalized cancer vaccine for treating a cancerous subject in need thereof. A specific embodiment is directed to a method of providing such a vaccine or composition comprising an identification step comprising a) extracting the DNA from a tumor sample and a non-tumor sample, b) selecting target regions, c) sequencing the target regions from the extracted DNAs and d) identifying one or more tumor-specific mutation(s) by comparing the DNA sequences obtained from the tumor and non-tumor samples. Embodiments also include a method of treating cancer or preventing its relapse comprising administration of such a personalized cancer vaccine. The invention is of very special interest in the field of personalized immunotherapy.