Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2018; 24(48): 5418-5432
Published online Dec 28, 2018. doi: 10.3748/wjg.v24.i48.5418
Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens
Sandra Wagner, Christina S Mullins, Michael Linnebacher
Sandra Wagner, Christina S Mullins, Michael Linnebacher, Section of Molecular Oncology and Immunotherapy, General Surgery, University Medical Center, Rostock D-18057, Germany
Author contributions: Wagner S and Linnebacher M wrote the manuscript and critically reviewed the final version of the manuscript. Mullins CS was involved in the design of the figures; critically reviewed the revised manuscript and language edited the manuscript as a native speaker.
Supported by Ministerium für Wirtschaft, Arbeit und Gesundheit Mecklenburg-Vorpommern, No. TBI-V-1-241-VBW-084.
Conflict-of-interest statement: Ms. Wagner has nothing to disclose. Dr. Mullins is supported by the Robert Bosch Stiftung with a Fast Track scholarship. Dr. Linnebacher reports grants from Ministerium für Wirtschaft, Arbeit und Gesundheit Mecklenburg-Vorpommern, during the conduct of the study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Michael Linnebacher, PhD, Academic Fellow, Department of General Surgery, Section of Molecular Oncology and Immunotherapy, University Medical Center, Schillingallee 35, Rostock D-18057, Germany.
Telephone: +49-381-4946043 Fax: +49-381-4946002
Received: October 13, 2018
Peer-review started: October 14, 2018
First decision: November 8, 2018
Revised: December 11, 2018
Accepted: December 20, 2018
Article in press: December 21, 2018
Published online: December 28, 2018

Therapeutic options for the treatment of colorectal cancer (CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hyper-mutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens (TAAs) and tumor-specific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptide-based vaccines achievable by adjuvants and immune-stimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens - in CRC almost exclusively neoantigens - which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immune-stimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine’s requirements and will manifest as treatment pillar for routine clinical management of CRC.

Keywords: Cancer vaccines, Colorectal neoplasm, Immunotherapy, Neoplasm antigen, Tumor-associated antigens, Tumor-specific antigens, Neoantigen(s)

Core tip: Peptide vaccines are a promising tool for colorectal cancer (CRC) treatment. Direct comparison of tumor-associated antigens (TAAs) and neoantigens reveals clear superiority of the latter for several reasons. TAAs, albeit easier to identify and even shared by many patients, did not prove effective in clinical trials. Additionally, and due to their unspecificity, they frequently trigger severe adverse events. This risk is neglectable for tumor-specific neoantigens - thus compensating for the costly and laborious identification of such antigens expressed in individual patient tumors. Intelligent modern CRC vaccines will likely combine several or even many individual neoantigen-derived peptides with immuno-chemotherapy, adjuvants or further immuno-modulators.