Liquid Biopsy Biomarkers for Immunotherapy in Non-Small Cell Lung Carcinoma: Lessons Learned and the Road Ahead

Hita-Millan, Jesus; Carracedo, Ángel; Fernández–Rozadilla, Ceres

doi:10.3390/jpm11100971

Cited by 5 publications

(2 citation statements)

References 141 publications

(156 reference statements)

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“…Treatment with CCX559 increased the level of plasma sPD-L1, which reflects both exosomal PD-L1 and the extracellular domain that is shed from the cell surface by matrix metalloproteases. Increased blood levels of sPD-L1 have been observed in cancer, autoimmunity, inflammation, and pregnancy [ 1 , 22 ], possibly as a consequence of PD-L1’s role in maintaining peripheral homeostasis [ 1 , 23 ]. A number of cytokines, including IFNγ, have been shown to increase sPD-L1 levels in vitro and in vivo [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity

et al. 2023

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The interaction of PD-L1 with PD-1 is a major immune checkpoint that limits effector T cell function against cancer cells; monoclonal antibodies that block this pathway have been approved in multiple tumor indications. As a next generation therapy, small molecule inhibitors of PD-L1 have inherent drug properties that may be advantageous for certain patient populations compared to antibody therapies. In this report we present the pharmacology of the orally-available, small molecule PD-L1 inhibitor CCX559 for cancer immunotherapy. CCX559 potently and selectively inhibited PD-L1 binding to PD-1 and CD80 in vitro, and increased activation of primary human T cells in a T cell receptor-dependent fashion. Oral administration of CCX559 demonstrated anti-tumor activity similar to an anti-human PD-L1 antibody in two murine tumor models. Treatment of cells with CCX559 induced PD-L1 dimer formation and internalization, which prevented interaction with PD-1. Cell surface PD-L1 expression recovered in MC38 tumors upon CCX559 clearance post dosing. In a cynomolgus monkey pharmacodynamic study, CCX559 increased plasma levels of soluble PD-L1. These results support the clinical development of CCX559 for solid tumors; CCX559 is currently in a Phase 1, first in patient, multicenter, open-label, dose-escalation study (ACTRN12621001342808).

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Section: Discussionmentioning

confidence: 99%

CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity

et al. 2023

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“…Wang et al [279] have demonstrated that it is necessary a high-quality DNA to avoid underestimation of TMB for a correct clinical evaluation. Chauhan et al [280] have detected and calculated the TMB from the ctDNA in urine rather than in blood [281]. Although many different guidelines (such as NCCN and ESMO guidelines) do not address plasma-based testing TMB or other tumor agnostic biomarkers like neurotrophic tyrosine receptor kinase (NTRK), the ctDNA analysis can help to choose the best treatment in selected cases [194].…”

Section: Treatment Selection and Resistant Mechanismsmentioning

confidence: 99%

Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer

Caputo

Ciardiello

Corte

et al. 2023

Exploration of Targeted Anti-Tumor Therapy

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Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating biomarkers and circulating tumor DNA (ctDNA) is the preferred one. Nevertheless, tissue biopsy remains the gold standard for molecular evaluation of solid tumors whereas liquid biopsy is a complementary tool in many different clinical settings, such as treatment selection, monitoring treatment response, cancer clonal evolution, prognostic evaluation, as well as the detection of early disease and minimal residual disease (MRD). A wide number of technologies have been developed with the aim of increasing their sensitivity and specificity with acceptable costs. Moreover, several preclinical and clinical studies have been conducted to better understand liquid biopsy clinical utility. Anyway, several issues are still a limitation of its use such as false positive and negative results, results interpretation, and standardization of the panel tests. Although there has been rapid development of the research in these fields and recent advances in the clinical setting, many clinical trials and studies are still needed to make liquid biopsy an instrument of clinical routine. This review provides an overview of the current and future clinical applications and opening questions of liquid biopsy in different oncological settings, with particular attention to ctDNA liquid biopsy.

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Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

Yang

Chen

et al. 2023

Cell Death Dis

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Non-small cell lung cancer (NSCLC) is one of the most threatening malignancies to human health and life. In most cases, patients with NSCLC are already at an advanced stage when they are diagnosed. In recent years, lung cancer has made great progress in precision therapy, but the efficacy of immunotherapy is unstable, and its response rate varies from patient to patient. Several biomarkers have been proposed to predict the outcomes of immunotherapy, such as programmed cell death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). Nevertheless, the detection assays are invasive and demanding on tumor tissue. To effectively predict the outcomes of immunotherapy, novel biomarkers are needed to improve the performance of conventional biomarkers. Liquid biopsy is to capture and detect circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes in body fluids, such as blood, saliva, urine, pleural fluid and cerebrospinal fluid as samples from patients, so as to make analysis and diagnosis of cancer and other diseases. The application of liquid biopsy provides a new possible solution, as it has several advantages such as non-invasive, real-time dynamic monitoring, and overcoming tumor heterogeneity. Liquid biopsy has shown predictive value in immunotherapy, significantly improving the precision treatment of lung cancer patients. Herein, we review the application of liquid biopsy in predicting the outcomes of immunotherapy in NSCLC patients, and discuss the challenges and future directions in this field.

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Liquid Biopsy Biomarkers for Immunotherapy in Non-Small Cell Lung Carcinoma: Lessons Learned and the Road Ahead

Cited by 5 publications

References 141 publications

CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity

CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity

Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

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