Xenograft cancer vaccines prepared from immunodeficient mice increase tumor antigen diversity and host T cell efficiency against colorectal cancers

Autologous cancer vaccines (ACVs) are a desirable approach for personalized medicine, but the efficiency of ACVs remains unsatisfactory due to their low immunogenicity. This study developed a platform that can enhance the immunogenicity of ACVs by transplanting the tumors into immunodeficient mice. The CT26 cell line was inoculated into severe combined immunodeficient mice (SCID) for vaccine preparation where escalates tumor development, subsequently diversifying the tumor antigenic topology. CT26/SCID cancer vaccines significantly inhibited tumor growth, increased the amount of tumor infiltrating lymphocytes, and triggered Th-1 predominant immune responses. Tumor antigenic profiles of CT26/SCID cells were further analyzed by liquid chromatography-tandem mass spectrometry. Compared to CT26 parental cells, a total of 428 differentially expressed proteins (DEPs) were detected. These DEPs revealed that CT26/SCID cells overexpressed several novel therapeutic targets, including KNG1, apoA-I and, beta 2-GPI, which can trigger cytotoxic T cells towards Th-1 predominant immune responses and directly suppress proliferation in tumors. CT26/SCID cancer vaccines can be easily manufactured, while traits of triggering stronger antigen-specific Th-1 immune activity against tumors, are retained. Results of this study provide an effective proof-of-concept of an ACV for personalized cancer immunotherapy.

Automated summary

A platform was developed to enhance the immunogenicity of autologous cancer vaccines by transplanting tumors into immunodeficient mice, leading to diversified tumor antigenic topology. CT26/SCID cancer vaccines inhibited tumor growth, increased tumor infiltrating lymphocytes, and triggered Th-1 predominant immune responses. Notably, differentially expressed proteins in CT26/SCID cells revealed novel therapeutic targets that can stimulate cytotoxic T cells and suppress tumor proliferation. This study provides effective proof-of-concept for personalized cancer immunotherapy using ACVs.