Cancer neoantigens as potential targets for immunotherapy

Abstract

Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programed cell death protein 1 (PD-1) or its ligand PD-L1 have increased the survival and cure rates for patients with many cancer types in various disease settings. However, only 10–40% of cancer patients benefited from these ICIs, of whom ~ 20% have treatment interruption or discontinuation due to immune-related adverse events that can be severe and even fatal. Current efforts in precision immunotherapy are focused on improving biomarker-based patient selection for currently available ICIs and exploring rationale combination and novel strategies to expand the benefit of immunotherapy to more cancer patients. Neoantigens arise from ~ 10% of the non-synonymous somatic mutations in cancer cells, are important targets of T cell-mediated anti-tumor immunity for individual patients. Advances in next generation sequencing technology and computational bioinformatics have enable the identification of genomic alterations, putative neoantigens, and gene expression profiling in individual tumors for personal oncology in a rapid and cost-effective way. Among the genomic biomarkers, defective mismatch DNA repair (dMMR), microsatellite instability high (MSI-H) and high tumor mutational burden (H-TMB) have received FDA approvals for selecting patients for ICI treatment. All these biomarkers measure high neoantigen load and tumor antigenicity, supporting the current development of neoantigen-based personalized cancer vaccines for patients with high TMB tumor. Several studies have shown neoantigen vaccines are feasible, safe and have promising clinical activity in patients with high TMB tumors in both metastatic and adjuvant settings. This review summarizes the emerging data and technologies for neoantigen-based personalized immunotherapy.

CCR4 as a Therapeutic Target for Cancer Immunotherapy

“…Cancer cells can be recognized by the host immune system through the expression of cancer antigens such as cancer differentiation antigens, cancer testis antigens, and cancer neoantigens. In particular, cancer neoantigens are generated as the consequence of genetic damage accumulated during cancer progression and provide ideal immunological targets for host CD4 + and CD8 + T cells [ 190 , 191 ]. Thus, the host immune system can potentially eliminate autologous tumor cells.…”

Topology and adenocarcinoma cell localization dataset on the labyrinthin biomarker

“… Because identification and characterization of neoantigens [3, 4, 5] are rare yet increasingly important for diagnostics and therapeutics, the identification of labyrinthin as a pan-adenocarcinoma target is significant for further study by clinicians and cancer researchers. The data provide a basis to determine to what extent labyrinthin is a distinguishing marker for adenocarcinomas vs. conventional methods. The results indicate that therapeutic strategies can be employed that take advantage of labyrinthin’s convenient presence on adenocarcinoma cell surfaces. The discovery of a calcium binding sequence in labyrinthin provides a basis to research if it is key to explaining the long-known phenomena of elevated calcium and irregular signaling in cancer cells [8, 9]. The data reveal a need to explore distinctions between ASPH and labyrinthin, in particular because ASPH [10, 11] and labyrinthin-based treatments have already been FDA approved for clinical trials. …”

“…Because identification and characterization of neoantigens [3, 4, 5] are rare yet increasingly important for diagnostics and therapeutics, the identification of labyrinthin as a pan-adenocarcinoma target is significant for further study by clinicians and cancer researchers.…”

“…Identification and characterization of neoantigens [3, 4] such as labyrinthin [5] are rare yet increasingly important for cancer treatment. Insight on labyrinthin as a pan-adenocarcinoma target labyrinthin for clinicians and cancer researchers is provided and consistent with 1) the convenient location of labyrinthin on the cell surface of adenocarcinomas; 2) appearance throughout the A549 human lung adenocarcinoma cell cycle; and 3) not modulated from the cell surface.…”

Introduction: Novel Frontiers in Cancer Metastasis

“…The last conference in 2017 was summarized in a special issue by Clinical and Experimental Metastasis [ 1 ]. The 8th International Cancer Metastasis Congress in October 2019 in San Francisco [ 2 ] addressed four major themes including cancer heterogeneity due to mutation [ 3 , 4 ] with association of formation of neoantigens [ 5 , 6 ], cancer progression relating to the cancer microenvironment and the mechanisms of metastasis through the lymphatic versus blood vessels and cancer therapy. These major topics are covered in 23 review articles being published online and they have been incorporated into this Special Issue: Novel Frontiers in Cancer Metastasis [ 7 ].…”