TY - CHAP
T1 - Beyond Sequencing
T2 - Prioritizing and Delivering Neoantigens for Cancer Vaccines
AU - Roesler, Alexander S.
AU - Anderson, Karen S.
N1 - Funding Information:
Funding: This work was supported by the Breast Cancer Research Foundation (KSA) and the Mayo Clinic Zicarelli Fund (KSA and ASR).
Publisher Copyright:
© 2022, The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022
Y1 - 2022
N2 - Neoantigens are tumor-specific proteins and peptides that can be highly immunogenic. Immune-mediated tumor rejection is strongly associated with cytotoxic responses to neoantigen-derived peptides in noncovalent association with self-HLA molecules. Neoantigen-based therapies, such as adoptive T cell transfer, have shown the potential to induce remission of treatment-resistant metastatic disease in select patients. Cancer vaccines are similarly designed to elicit or amplify antigen-specific T cell populations and stimulate directed antitumor immunity, but the selection and prioritization of the neoantigens remains a challenge. Bioinformatic algorithms can predict tumor neoantigens from somatic mutations, insertion-deletions, and other aberrant peptide products, but this often leads to hundreds of potential neoepitopes, all unique for that tumor. Selecting neoantigens for cancer vaccines is complicated by the technical challenges of neoepitope discovery, the diversity of HLA molecules, and intratumoral heterogeneity of passenger mutations leading to immune escape. Despite strong preclinical evidence, few neoantigen cancer vaccines tested in vivo have generated epitope-specific T cell populations, suggesting suboptimal immune system activation. In this chapter, we review factors affecting the prioritization and delivery of candidate neoantigens in the design of therapeutic and preventive cancer vaccines and consider synergism with standard chemotherapies.
AB - Neoantigens are tumor-specific proteins and peptides that can be highly immunogenic. Immune-mediated tumor rejection is strongly associated with cytotoxic responses to neoantigen-derived peptides in noncovalent association with self-HLA molecules. Neoantigen-based therapies, such as adoptive T cell transfer, have shown the potential to induce remission of treatment-resistant metastatic disease in select patients. Cancer vaccines are similarly designed to elicit or amplify antigen-specific T cell populations and stimulate directed antitumor immunity, but the selection and prioritization of the neoantigens remains a challenge. Bioinformatic algorithms can predict tumor neoantigens from somatic mutations, insertion-deletions, and other aberrant peptide products, but this often leads to hundreds of potential neoepitopes, all unique for that tumor. Selecting neoantigens for cancer vaccines is complicated by the technical challenges of neoepitope discovery, the diversity of HLA molecules, and intratumoral heterogeneity of passenger mutations leading to immune escape. Despite strong preclinical evidence, few neoantigen cancer vaccines tested in vivo have generated epitope-specific T cell populations, suggesting suboptimal immune system activation. In this chapter, we review factors affecting the prioritization and delivery of candidate neoantigens in the design of therapeutic and preventive cancer vaccines and consider synergism with standard chemotherapies.
KW - Cancer immunotherapy
KW - Cancer vaccine
KW - Neoantigen
KW - Nucleic acid vaccine
KW - RNA vaccine
KW - Synthetic long peptide vaccine
KW - Vaccine delivery
KW - Vaccine formulation
UR - http://www.scopus.com/inward/record.url?scp=85121634939&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121634939&partnerID=8YFLogxK
U2 - 10.1007/978-1-0716-1884-4_35
DO - 10.1007/978-1-0716-1884-4_35
M3 - Chapter
C2 - 34914074
AN - SCOPUS:85121634939
T3 - Methods in Molecular Biology
SP - 649
EP - 670
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -