scholarly journals Identification of Tumor Specific Neoantigens and Their Implications in Dendritic Cell Immunotherapy Using Liquid Biopsy Results: Findings from an Observational Cohort Study

2021 ◽  
Author(s):  
Khin Zay Yar Myint ◽  
Masamori Shimabuku ◽  
Ruriko Horio ◽  
Munehisa Kaneda ◽  
Yoko Shimizu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Liquid Biopsy ◽  
Clonal Evolution ◽  
Cost Effective ◽  
Average Frequency ◽  
Liquid Biopsies ◽  
Genetic Profiling ◽  
Cell Immunotherapy ◽  
Observational Cohort ◽  
Tumor Biopsies

Abstract Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using neoantigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for neoantigen-based immunotherapy and the importance of tailoring neoantigen-based immunotherapy in accordance with the liquid biopsy result in each treatment stage.

scholarly journals Identification of Tumor Specific Neoantigens and Their Implications in Dendritic Cell Immunotherapy Using Liquid Biopsy Results: Findings from an Observational Cohort Study

2021 ◽  
Author(s):  
Khin Zay Yar Myint ◽  
Masanari Shimabuku ◽  
Ruriko Horio ◽  
Munehisa Kaneda ◽  
Yoko Shimizu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Liquid Biopsy ◽  
Clonal Evolution ◽  
Cost Effective ◽  
Average Frequency ◽  
Liquid Biopsies ◽  
Genetic Profiling ◽  
Cell Immunotherapy ◽  
Observational Cohort ◽  
Tumor Biopsies

Abstract Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using neoantigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for neoantigen-based immunotherapy and the importance of tailoring neoantigen-based immunotherapy in accordance with the liquid biopsy result in each treatment stage.

scholarly journals Identification of Tumor Specific Neoantigens and Their Implications in Dendritic Cell Immunotherapy Using Liquid Biopsy Results: Findings from an Observational Cohort Study

2021 ◽  
Author(s):  
Khin Zay Yar Myint ◽  
Masamori Shimabuku ◽  
Ruriko Horio ◽  
Munehisa Kaneda ◽  
Yoko Shimizu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Liquid Biopsy ◽  
Clonal Evolution ◽  
Specific Antigen ◽  
Cost Effective ◽  
Average Frequency ◽  
Liquid Biopsies ◽  
Genetic Profiling ◽  
Cell Immunotherapy ◽  
Tumor Biopsies

Abstract Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using these antigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for tumor-specific antigen-based immunotherapy and the importance of tailoring immunotherapy in accordance with the liquid biopsy result in each treatment stage.

scholarly journals Circulating Tumor DNA as a Liquid Biopsy for Cancer

2015 ◽  
Vol 61 (1) ◽  
pp. 112-123 ◽  
Author(s):  
Ellen Heitzer ◽  
Peter Ulz ◽  
Jochen B Geigl
Keyword(s):  
Liquid Biopsy ◽  
Dna Analysis ◽  
Clonal Evolution ◽  
Cost Effective ◽  
Circulating Tumor Dna ◽  
Analytical Sensitivity ◽  
Plasma Dna ◽  
Multicenter Studies ◽  
Almost All ◽  
Tumor Dna

Abstract BACKGROUND Targeted therapies have markedly changed the treatment of cancer over the past 10 years. However, almost all tumors acquire resistance to systemic treatment as a result of tumor heterogeneity, clonal evolution, and selection. Although genotyping is the most currently used method for categorizing tumors for clinical decisions, tumor tissues provide only a snapshot, or are often difficult to obtain. To overcome these issues, methods are needed for a rapid, cost-effective, and noninvasive identification of biomarkers at various time points during the course of disease. Because cell-free circulating tumor DNA (ctDNA) is a potential surrogate for the entire tumor genome, the use of ctDNA as a liquid biopsy may help to obtain the genetic follow-up data that are urgently needed. CONTENT This review includes recent studies exploring the diagnostic, prognostic, and predictive potential of ctDNA as a liquid biopsy in cancer. In addition, it covers biological and technical aspects, including recent advances in the analytical sensitivity and accuracy of DNA analysis as well as hurdles that have to be overcome before implementation into clinical routine. SUMMARY Although the analysis of ctDNA is a promising area, and despite all efforts to develop suitable tools for a comprehensive analysis of tumor genomes from plasma DNA, the liquid biopsy is not yet routinely used as a clinical application. Harmonization of preanalytical and analytical procedures is needed to provide clinical standards to validate the liquid biopsy as a clinical biomarker in well-designed and sufficiently powered multicenter studies.

scholarly journals Clonal evolution in the transition from cutaneous disease to acute leukemia suggested by liquid biopsy in blastic plasmacytoid dendritic cell neoplasm

Haematologica ◽  
2018 ◽  
Vol 103 (5) ◽  
pp. e196-e199 ◽  
Author(s):  
Eleni Ladikou ◽  
Barbara Ottolini ◽  
Nadia Nawaz ◽  
Rebecca L. Allchin ◽  
Daniel Payne ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Acute Leukemia ◽  
Liquid Biopsy ◽  
Clonal Evolution ◽  
Plasmacytoid Dendritic Cell ◽  
Cutaneous Disease ◽  
Cell Neoplasm

scholarly journals Liquid biopsy assessment of synchronous malignancies: a case report and review of the literature

ESMO Open ◽  
2019 ◽  
Vol 4 (4) ◽  
pp. e000528 ◽  
Author(s):  
Sandra Liebs ◽  
Anika Nonnenmacher ◽  
Frederick Klauschen ◽  
Ulrich Keilholz ◽  
Loredana Vecchione
Keyword(s):  
Case Report ◽  
Liquid Biopsy ◽  
Disease Surveillance ◽  
Clonal Evolution ◽  
Multiple Primary Cancers ◽  
Review Of The Literature ◽  
Liquid Biopsies ◽  
Cancer Management ◽  
Pancreatic Tumour ◽  
Synchronous Malignancies

Assessment of patients with synchronous primary cancers and metastases is challenging, as it can be difficult to assign the metastases to the correct primary due to low differentiation, high similarity on histology or inaccessibility of tumour tissue. Systemic treatment for metastatic disease, however, needs to be directed at the leading histology or cover multiple tumour types with the same regimen. Considering the additional obstacles in cancer management, including tumour heterogeneity and clonal evolution, blood-based genomic profiling (‘liquid biopsy’) is suggested to be a useful tool to provide accessible tumour-derived biomarkers. We herein report a case of a patient with independent primary tumours of the colon and pancreas, as well as liver metastases. All lesions were resected and genotyped revealing KRAS mutations G12C and G12D in the primary tumours, respectively. The G12D mutation detected in the pancreatic tumour was retrieved in the metastasis, thus confirming the pancreatic cancer to be the origin of the liver lesions. The prevalence of the pancreatic tumour was additionally verified by the detection of the G12D variant in circulating cell-free DNA (cfDNA). This case demonstrates the utility of liquid biopsy to identify the predominant tumour burden in patients with multiple primary cancers, based on the detection of the tumour-associated gene mutation in the plasma. Serial monitoring through liquid biopsies might allow disease surveillance to guide cancer management. The review of the literature highlights the importance of liquid biopsies in personalised oncology, even though only one case report refers to the benefit of cfDNA analysis in a patient affected by synchronous primary tumours.

scholarly journals NGS Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Melanoma Samples Using Oncomine™ Pan-Cancer Cell-Free Assay

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1080
Author(s):  
Magdalena Olbryt ◽  
Marcin Rajczykowski ◽  
Wiesław Bal ◽  
Anna Fiszer-Kierzkowska ◽  
Alexander Jorge Cortez ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Liquid Biopsy ◽  
High Sensitivity ◽  
Genetic Profile ◽  
Liquid Biopsies ◽  
Braf Mutations ◽  
Genetic Profiling ◽  
Pathogenic Variants ◽  
Ffpe Tumor ◽  
Pan Cancer

Next-generation sequencing (NGS) in liquid biopsies may contribute to the diagnosis, monitoring, and personalized therapy of cancer through the real-time detection of a tumor’s genetic profile. There are a few NGS platforms offering high-sensitivity sequencing of cell-free DNA (cfDNA) samples. The aim of this study was to evaluate the Ion AmpliSeq HD Technology for targeted sequencing of tumor and liquid biopsy samples from patients with fourth-stage melanoma. Sequencing of 30 samples (FFPE tumor and liquid biopsy) derived from 14 patients using the Oncomine™ Pan-Cancer Cell-Free Assay was performed. The analysis revealed high concordance between the qPCR and NGS results of the BRAF mutation in FFPE samples (91%), as well as between the FFPE and liquid biopsy samples (91%). The plasma-tumor concordance of the non-BRAF mutations was 28%. A total of 17 pathogenic variants in 14 genes (from 52-gene panel), including TP53, CTNNB1, CCND1, MET, MAP2K1, and GNAS, were identified, with the CTNNB1S45F variant being the most frequent. A positive correlation between the LDH level and cfDNA concentration as well as negative correlation between the LDH level and time to progression was confirmed in a 22-patient cohort. The analysis showed both the potential and limitations of liquid biopsy genetic profiling using HD technology and the Ion Torrent platform.

scholarly journals Clonal evolution of colorectal cancer in a patient with serially resected metastases and liquid biopsies: a case report and discussion of the literature

ESMO Open ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. e000329 ◽  
Author(s):  
Myrto Kastrisiou ◽  
George Zarkavelis ◽  
Eleftherios Kampletsas ◽  
Eleni Panopoulou ◽  
Anna Goussia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liquid Biopsy ◽  
Clonal Evolution ◽  
Primary Tumour ◽  
Acquired Resistance ◽  
Liquid Biopsies ◽  
Clonal Heterogeneity ◽  
Clinical Endpoints ◽  
Multiple Metastases ◽  
Metastatic Sites

BackgroundMetastatic colorectal cancer represents a striking example of clonal heterogeneity and tumour evolution, which generates acquired resistance to therapy. Once hard to perform, the study of clonal heterogeneity is now significantly aided by the use of liquid biopsies.MethodWe herein report a case of a patient with colorectal cancer and serial development of multiple metastases which were all resected and genotyped. A rare point mutation was identified in the primary tumour (but not in any of the organ metastatic sites), as well as in the first and the last out of three consecutive liquid biopsies. The review of the literature offered some insight in the evolution of the patient’s tumour and general directions on how to interpret liquid biopsy results.ConclusionsThis patient case emphasises the need for large prospective studies designed to bridge liquid biopsy data with useful clinical endpoints, in order to optimally integrate this revolutionary tool in everyday practice.

scholarly journals The Liquid Biopsy for Lung Cancer: State of the Art, Limitations and Future Developments

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3923
Author(s):  
Daniel Di Capua ◽  
Dara Bracken-Clarke ◽  
Karine Ronan ◽  
Anne-Marie Baird ◽  
Stephen Finn
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Targeted Therapies ◽  
Liquid Biopsy ◽  
Genetic Alterations ◽  
Rapid Progression ◽  
Liquid Biopsies ◽  
Cell Lung Carcinoma ◽  
Genetic Sequencing ◽  
Tissue Biopsy

Lung cancer is a leading cause of cancer-related deaths, contributing to 18.4% of cancer deaths globally. Treatment of non-small cell lung carcinoma has seen rapid progression with targeted therapies tailored to specific genetic drivers. However, identifying genetic alterations can be difficult due to lack of tissue, inaccessible tumors and the risk of complications for the patient with serial tissue sampling. The liquid biopsy provides a minimally invasive method which can obtain circulating biomarkers shed from the tumor and could be a safer alternative to tissue biopsy. While tissue biopsy remains the gold standard, liquid biopsies could be very beneficial where serial sampling is required, such as monitoring disease progression or development of resistance mutations to current targeted therapies. Liquid biopsies also have a potential role in identifying patients at risk of relapse post treatment and as a component of future lung cancer screening protocols. Rapid developments have led to multiple platforms for isolating circulating tumor cells (CTCs) and detecting circulating tumor DNA (ctDNA); however, standardization is lacking, especially in lung carcinoma. Additionally, clonal hematopoiesis of uncertain clinical significance must be taken into consideration in genetic sequencing, as it introduces the potential for false positives. Various biomarkers have been investigated in liquid biopsies; however, in this review, we will concentrate on the current use of ctDNA and CTCs, focusing on the clinical relevance, current and possible future applications and limitations of each.

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