Immunopharmacogenomics towards personalized cancer immunotherapy targeting neoantigens

Abstract

Utilizing the host immune system to eradicate cancer cells has been the most investigated subject in the cancer research field in recent years. However, most of the studies have focused on highly variable responses from immunotherapies such as immune checkpoint inhibitors, from which the majority of patients experienced no or minimum clinical benefit. Advances in genomic sequencing technologies have improved our understanding of immunopharmacogenomics and allowed us to identify novel cancer‐specific immune targets. Highly tumor‐specific antigens, neoantigens, are generated by somatic mutations that are not present in normal cells. It is plausible that by targeting antigens with high tumor‐specificity, such as neoantigens, the likelihood of toxic effects is very limited. However, understanding the interaction between neoantigens and the host immune system remains a significant challenge. This review focuses on the potential use of neoantigen‐targeted immunotherapies in cancer treatment and the recent progress of different strategies in predicting, identifying, and validating neoantigens. Successful identification of highly tumor‐specific antigens accelerates the development of personalized immunotherapy with no or minimum adverse effects and with a broader coverage of patients.

Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer

“…The prediction of neoantigen from whole‐exome data was done using an in‐house pipeline as described previously. Briefly, the four‐digit HLA type for each sample was determined using the OptiType algorithm.…”

Significant differences in T cell receptor repertoires in lung adenocarcinomas with and without epidermal growth factor receptor mutations

“…Human leukocyte antigen (HLA) class I genotypes were determined using the WES data of normal tissues and the OptiType algorithm . Neoantigens were predicted for each non‐synonymous variant by defining all 8‐mer to 11‐mer peptides resulting from the mutation and determining the predicted binding affinity to HLA‐A, B and C of <500 nM, using NetMHCv3.4 and NetMHCpanv2.8 software …”

“…The progress in analyzing T cell receptor (TCR) repertoires in cancer tissues made it possible to evaluate the diversity of T cell clonotypes and the extent of clonal T cell expansion, and to characterize neoantigen‐specific TCR . Detailed information on the tumor microenvironment may serve as a predictive marker for immunomodulatory therapies and may also be useful for development of new treatment strategies, including personalized T cell‐mediated cancer immunotherapy and neoantigen vaccine therapy . TCR repertoire analyses could be used to monitor the dynamics of T cell clonality and the individual tumor‐reactive T cell clones in cancer patients treated with ICI .…”

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

“…Adaptive immunity in ovarian cancer is rapidly expanding to enhance dendritic cell (DC)-mediated presentation of ovarian cancer, predominantly by vaccination ( 45 , 46 ) ( Figure 1 ). Cytotoxic T lymphocytes (CTLs) are activated after recognizing tumor-associated antigens (TAAs), and particularly the neoantigens ( 47 ). Ovarian cancer tumor cells often evade destruction by CTLs through inhibitory signals in the tumor ( 48 ).…”