Personalized Cancer Vaccines Go Viral: Viral Vectors in the Era of Personalized Immunotherapy of Cancer

Abstract

The aim of personalized cancer vaccines is to elicit potent and tumor-specific immune responses against neoantigens specific to each patient and to establish durable immunity, while minimizing the adverse events. Over recent years, there has been a renewed interest in personalized cancer vaccines, primarily due to the advancement of innovative technologies for the identification of neoantigens and novel vaccine delivery platforms. Here, we review the emerging field of personalized cancer vaccination, with a focus on the use of viral vectors as a vaccine platform. The recent advancements in viral vector technology have led to the development of efficient production processes, positioning personalized viral vaccines as one of the preferred technologies. Many clinical trials have shown the feasibility, safety, immunogenicity and, more recently, preliminary evidence of the anti-tumor activity of personalized vaccination, fostering active research in the field, including further clinical trials for different tumor types and in different clinical settings.

Keywords: adenovirus; neoantigens; personalized cancer vaccines; poxvirus; viral vectors.

Figure 1

Mechanism of action of personalized cancer vaccine. After vaccination at the injection site, Dendritic Cells (DCs) or other Antigen-Presenting Cells (APCs) are loaded with antigens and migrate to the draining lymph node. There, the APCs present the antigens through the Major Histocompatibility Complex classes I (MHC I) and II (MHC II), respectively, to the CD8 and CD4 T cells. The activated T cells with an antigen-specific T cell receptor (TCR) proliferate and migrate to the tumor microenvironment (TME), where they recognize and kill cancer cells through the release of cytotoxic granules.

Figure 2

Engineering individualized neoantigen vaccines. The next-generation sequencing of a patient’s healthy tissue (such as peripheral blood mononuclear cells (PBMCs)) and a tumor biopsy sample is performed. The sequenced data from tumor and normal DNA are compared to identify the tumor-specific mutations. The mutations are prioritized as vaccine candidates on the basis of their likelihood to elicit a T cell response via computational methods, such as human leukocyte antigen (HLA)-binding prediction, the quantification of mutated transcript expression, and the clonality of the mutation and other features.

Figure 3

Manufacturing workflow of viral vector-based personalized cancer vaccines. Specimens (tumor and normal) are collected at the clinical site and shipped for next-generation sequencing (NGS) analysis. Subsequently, both the DNA and RNA undergo next-generation sequencing, which is followed by computational analysis, variant calls, neoantigen prioritization, and poly-neoepitope design. A viral vector is then constructed, and small-scale Good Manufacturing Practice (GMP) and analytical control processes are performed, leading to Quality Assurance/Quality person (QA/QP) release. Finally, the drug product is shipped to the clinical site for patient administration.