ABSTRACT: Efficient identification of a novel cancer/testis antigen as a candidate of cancer immunotherapy using three-step microarray analysis (CBX37)
Project description:Background: Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to testis tissues, but aberrantly high expressed in a variety of cancer tissues. In view of this, CTAs are typically considered as efficient biomarkers and targets of immunotherapy. However, limited information is available regarding CTAs as immunotherapeutic targets for gastric cancer (GC) patients. Herein, we evaluated the expression levels of CTAs in both Eastern and Western GC patients and elucidate the expression pattern and functions of a novel CTAs.
Project description:Immunotherapy has shown great therapeutic potential for cancers with high tumor mutational burden (TMB), but much less promise for cancers with low TMB. One primary approach for adoptive lymphocyte transfer-based immunotherapy is to target the somatic mutated peptide neoantigens and cancer testis (CT) antigens recognized by cytotoxic T cells. Here, we employed mass spectrometry (MS)-based proteogenomic large-scale profiling to identify potential immunogenic human leukocyte antigen (HLA) Class ǀ- associated peptides in both melanoma, a “hot tumor”, and EGFR mutant lung adenocarcinoma, a “cold tumor”. We uncovered 19 common driver oncogene-derived peptides and more than 1000 post-translationally modified peptides (PTM) representing 58 different PTMs. We constructed a CT antigen database with 286 antigens by compiling reputed CT antigen resources and “in-house” genomic data and used this to identify 45 CT antigen-derived peptides from the identified HLA peptidome. Using integrated next generation sequencing data, we discovered 12 neopeptides in EGFR mutant lung cancer cell lines. Finally, we report a novel approach for non-canonical peptide discovery, whereby we leveraged a deep learning-based de novo search and a high confidence annotated long noncoding RNA (LncRNA) database to identify 44 lncRNA-derived peptides. Findings of this study, for the first time, provide evidence for a large pool of actionable cancer antigen-derived peptides for use in mutant EGFR lung cancer immunotherapy.
Project description:Analysis of gene expression data to evaluate candidate targets for immunotherapy. Analysis of gene expression data to evaluate candidate targets for immunotherapy, We analyse 7 lung cancer samples and 3 reference samples (2x kidney, 1x lung).
Project description:Current chemotherapy or immunotherapy regimens for pancreatic cancer are limited. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for unresectable pancreatic cancers, the typical immunosuppressive tumour microenvironment promotes immune evasion and rapid tumour recurrence. Thus, triggering efficient amplification of endogenous adaptive antitumour immunity is critical for improving immunotherapy after ablation therapy. Here, we developed a hydrogel microsphere vaccine as an immune amplifier for post-ablation cancer immunotherapy. The vaccine acts as a general immune amplifier to trigger a rocket-like amplification of the cDC1-mediated antigen cross-presentation cascade, resulting in dramatic amplification of the antitumour immunity of endogenous CD8+ T cells. We also showed that the hydrogel microsphere vaccine promoted the transformation of pancreatic cancer from "cold" to "hot" tumours in a safe and efficient manner, significantly increased the survival of mice bearing orthotopic pancreatic tumours, and induced strong systemic antitumour immunity, which inhibited the growth of distant metastases.
Project description:Tumour-associated macrophages (TAMs), as one of the most abundant and phagocytic tumour-infiltrating immune cells, play a pivotal role in tumour antigen clearance and immune suppression. M2-like TAMs present a heightened lysosomal acidity and protease activity, which limits the function of antigen cross-presentation. How to selectively reprogram the antigen-destroying TAMs to a restorative phenotype for efficient anti-tumour immunity is challenging. Here, we report a pH-gated nanoadjuvant (PGN) that selectively targets the lysosomes of M2-like TAMs in tumours rather than the corresponding organelles from macrophages in healthy tissues. Enabled by the PGN nanotechnology, M2-like TAMs are specifically switched to M1-like phenotypes with tuned-down lysosomal function featured by attenuated lysosomal acidity and cathepsin activity for improved antigen cross-presentation, thus provoking adaptive immune response and sustained tumour regression. Our findings provide new insights into how to specifically regulate lysosomal function of TAMs for efficient cancer immunotherapy.
