Mechanisms of drug resistance to immune checkpoint inhibitors in non-small cell lung cancer DOI Creative Commons
Kexun Zhou, Shuo Li, Yi Zhao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 8, 2023

Immune checkpoint inhibitors (ICIs) in the form of anti-CTLA-4 and anti-PD-1/PD-L1 have become frontier cancer treatment successfully prolonged survival patients with advanced non-small cell lung (NSCLC). But efficacy varies among different patient population, many succumb to disease progression after an initial response ICIs. Current research highlights heterogeneity resistance mechanisms critical role tumor microenvironment (TME) ICIs resistance. In this review, we discussed NSCLC, proposed strategies overcome

Language: Английский

The introduction of LAG-3 checkpoint blockade in melanoma: immunotherapy landscape beyond PD-1 and CTLA-4 inhibition DOI Creative Commons
Firas Kreidieh, Hussein A. Tawbi

Therapeutic Advances in Medical Oncology, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 1, 2023

Despite major advances with immunotherapy and targeted therapy in the past decade, metastatic melanoma continues to be a deadly disease for close half of all patients. Over advancement immune profiling deeper understanding tumor microenvironment (TME) have enabled development novel approaches targeting multitude targets being investigated melanoma. However, date, checkpoint blockade has remained most successful programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors, alone or combination, yielding robust durable clinical outcome patients The highest rate responses is achieved combination PD-1 CTLA-4 inhibition, effective variety settings including brain metastases; however, it comes at expense life-threatening toxicities occurring up 60% This also established as forefront immuno-oncology (IO) drug development, search checkpoints been ongoing multiple relevant T-cell immunoglobulin mucinodomain containing-3 (TIM-3), LAG-3, V-domain suppressor activation (VISTA), immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), among others. Lymphocyte gene-3 (LAG-3), which co-inhibitory receptor on T cells that suppress their activation, revolutionized immunomodulation 'game changing' results from RELATIVITY-047 trial validated LAG-3 biological target third clinically checkpoint. Importantly, inhibition offered impressive efficacy modest increases toxicity over single agent inhibitor U.S. Food Drug Administration approved first-line this untreated leptomeningeal metastases rare types, such uveal melanoma, remains established. challenge elucidate specific mechanisms response resistance extend its benefits other malignancies. Ongoing trials are studying antibodies inhibitors cancers settings. low may allow further layering additional therapeutic chemotherapy, oncolytic viruses, cellular therapies, possibly cytokines,

Language: Английский

Citations

41
Pembrolizumab for previously treated, microsatellite instability–high/mismatch repair–deficient advanced colorectal cancer: final analysis of KEYNOTE-164 DOI
Dung T. Le, Luis A. Díaz,

Tae Won Kim

et al.

European Journal of Cancer, Journal Year: 2023, Volume and Issue: 186, P. 185 - 195

Published: Feb. 25, 2023

Language: Английский

Citations

40
Immunotherapy-based combinations in metastatic NSCLC DOI Creative Commons
Aakash Desai, Solange Peters

Cancer Treatment Reviews, Journal Year: 2023, Volume and Issue: 116, P. 102545 - 102545

Published: March 27, 2023

Immuno-oncology has revolutionized the treatment of metastatic non-small cell lung cancer (mNSCLC) since approval immunotherapy by U.S. FDA in 2015. Despite advancements, outcomes for patients have room further improvement. Combination therapies shown promise overcoming resistance and improving outcomes. This review focuses on current immunotherapy-based combination approaches, reported ongoing trials, as well novel strategies, challenges, future directions mNSCLC treatment. We summarize approaches with chemotherapy, immune checkpoints, tyrosine kinase inhibitors other strategies including vaccines, radiation therapy. The biomarker-driven studies to understand design multi-arm platform trials that evaluate is becoming increasing relevance ultimate goal administering precision identifying right dose patient at time.

Language: Английский

Citations

36
Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors DOI Creative Commons
Tae Won Kim, Philippe L. Bédard,

Patricia LoRusso

et al.

JAMA Oncology, Journal Year: 2023, Volume and Issue: 9(11), P. 1574 - 1574

Published: Sept. 28, 2023

Importance Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify antitumor immune response atezolizumab in programmed death ligand 1–selected tumors. Objective To evaluate safety activity anti-TIGIT antibody tiragolumab its combination patients advanced solid Design, Setting, Participants The GO30103 open-label, first-in-human phase 1a/1b dose-escalation dose-expansion nonrandomized controlled trial was conducted at 13 sites 6 countries (Australia, Canada, France, Korea, Spain, US). start dates were May 23, 2016, for 1a October 11, 1b. Patients aged 18 years or older measurable disease baseline. clinical cutoff date 1, 2021. Data analysis performed on January 24, 2022. Interventions received fixed-dose intravenous day 1 each 21-day cycle (2 mg escalating to 1200 mg) 1a, plus (1200 every 3 weeks) treated until progression, loss benefit, development unacceptable toxicity. Main Outcomes Measures primary end points included safety, tolerability, recommended 2 dose (RP2D) atezolizumab. secondary point investigator-assessed objective rate (ORR). Counts percentages are used categorical variables, medians ranges continuous variables. Results Among (n = 24) 1b 49) cohorts, median age 60 (range, 40-77) 54 25-81) years, respectively. More than half women (14 24 [58%] 25 49 [51%]), more a third (10 [42%] [37%]) had 4 prior cancer therapies. No dose-limiting toxicities occurred, maximum tolerated not reached (NR). most frequent treatment-related adverse events (AEs) fatigue (5 [21%]) pruritus [10%]) 1b; majority AEs grade 2. Immune-mediated occurred (17%) 29 (59%) during phases 1b, respectively (primarily 2). RP2D 600 intravenously weeks, which tested expansion. confirmed ORR 0% evidence 6% 3) profile similar cohorts. 46% (6 13) non–small cell lung (NSCLC) cohort (median duration [DOR], NR) 28% 18) esophageal (EC) DOR, 15.2 [95% CI, 7.0 NR] months). Conclusions Relevance In this trial, well without atezolizumab; no new signals observed. Preliminary demonstrated regimen immunotherapy–naive metastatic NSCLC EC. Trial Registration ClinicalTrials.gov Identifier: NCT02794571

Language: Английский

Citations

35
Mechanisms of drug resistance to immune checkpoint inhibitors in non-small cell lung cancer DOI Creative Commons
Kexun Zhou, Shuo Li, Yi Zhao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 8, 2023

Immune checkpoint inhibitors (ICIs) in the form of anti-CTLA-4 and anti-PD-1/PD-L1 have become frontier cancer treatment successfully prolonged survival patients with advanced non-small cell lung (NSCLC). But efficacy varies among different patient population, many succumb to disease progression after an initial response ICIs. Current research highlights heterogeneity resistance mechanisms critical role tumor microenvironment (TME) ICIs resistance. In this review, we discussed NSCLC, proposed strategies overcome

Language: Английский

Citations

25