Therapeutic vaccines for advanced non?small cell lung cancer
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ABSTRACT:
SUBMITTER: Cortes?Jofre M
PROVIDER: S-EPMC6673723 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Project description:Non-small cell lung cancer (NSCLC) unfortunately carries a very poor prognosis. Patients usually do not become symptomatic, and therefore do not seek treatment, until the cancer is advanced and it is too late to employ curative treatment options. New therapeutic options are urgently needed for NSCLC, because even current targeted therapies cure very few patients. Active immunotherapy is an option that is gaining more attention. A delicate and complex interplay exists between the tumor and the immune system. Solid tumors utilize a variety of mechanisms to evade immune detection. However, if the immune system can be stimulated to recognize the tumor as foreign, tumor cells can be specifically eliminated with little systemic toxicity. A number of vaccines designed to boost immunity against NSCLC are currently undergoing investigation in phase III clinical trials. Belagenpumatucel-L, an allogeneic cell vaccine that decreases transforming growth factor (TGF-?) in the tumor microenvironment, releases the immune suppression caused by the tumor and it has shown efficacy in a wide array of patients with advanced NSCLC. Melanoma-associated antigen A3 (MAGE-A3), an antigen-based vaccine, has shown promising results in MAGE-A3(+) NSCLC patients who have undergone complete surgical resection. L-BLP25 and TG4010 are both antigenic vaccines that target the Mucin-1 protein (MUC-1), a proto-oncogene that is commonly mutated in solid tumors. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. These vaccines may significantly improve survival and quality of life for patients with an otherwise dismal NSCLC prognosis. This review is intended to give an overview of the current data and the most promising studies of active immunotherapy for NSCLC.
| S-EPMC4928356 | biostudies-other
Project description:Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor prognosis and no known cure. Survival time is often short because of limited treatment options. Recent advances in targeted therapy and immunotherapy have changed the landscape for the treatment of advanced NSCLC. In the last 10 years, the US Food and Drug Administration (FDA) has approved more than 17 new medications for this devastating disease and more are coming. Molecular and immunogenic testing makes personalized medicine possible for patients with advanced NSCLC. The new medications provide promising efficacy and safety resulting in improved long-term survival for a significant number of patients. In this review, we summarize the recent advances in advanced/metastatic NSCLC therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to current standard drugs in the same class or are a completely new class of drugs with novel mechanisms of action. Advances are divided into (1) targeted agents, (2) antibody-drug conjugates, and (3) immunotherapies. Finally, we present a brief review of the emerging agents and ongoing clinical studies.
| S-EPMC7245927 | biostudies-literature
Project description:AbstractImmune escape mechanisms in non-small cell lung cancer (NSCLC) can disrupt every step of the anti-cancer immune response. In recent years, an increased understanding of the specific mechanisms fueling immune escape has allowed for the development of numerous immunotherapeutic treatments that have been introduced into the clinical practice. The advent of immunotherapy has dramatically changed the current treatment landscape of advanced or metastatic NSCLC because of its durable efficacy and manageable toxicity. In this review, we will first present a brief overview of recent evidence on immune escape mechanisms in NSCLC. We will then discuss the current promising immunotherapeutic strategies in advanced or metastatic NSCLC tumors.
| S-EPMC10405997 | biostudies-literature
Project description:BackgroundEven after complete surgical treatment or chemotherapy, Non-Small Cell Lung Cancer (NSCLC) patients are also at substantial risk for recurrence and spread trend. Therapeutic cancer vaccination could increase the anti-tumor immune response and prevent tumor relapse. This study aimed to assess the characteristics of NSCLC therapeutic vaccines registered on ClinicalTrials.gov.MethodsWe conducted a cross-sectional, descriptive study of clinical trials for Non-Small Cell Lung Cancer Therapeutic Vaccines Registered on ClinicalTrials.gov (https://clinicaltrials.gov/) through March 17, 2022.ResultsThis study encompassed 117 registered trials included for data analysis. The number of trials was significantly correlated with a beginning year (r = 0.504, P < 0.010). Of these trials, 45.30% were completed, 12.82% were terminated, and 8.55% were withdrawn. More than half of trials (52.99%) were funded by industry, and more than half of trials (52.14%) were located in economically developed North America. Regarding study designs of these trials, 27.35% were randomized, 52.14% were single group assignment, 83.76% were without masking, 35.90% were phase 1, and more than half of the trials (56.41%) recruited less than 50 participants. The highest proportion of vaccine types was protein/peptide vaccines (41.88%). Regarding TNM staging, the highest proportion of the trials is stage III-IV (26.50%).ConclusionThe number of clinical trials about the cancer therapeutic vaccines was sustained an increase in recent years. The main characteristic of clinical trials for NSCLC therapeutic vaccines is lack of randomized control, lack of mask, and recruiting less than 50 participants. In recent years, the protein/peptide vaccines for NSCLC active immunotherapy have been well studied.
| S-EPMC9627174 | biostudies-literature
Project description:Small cell lung cancer (SCLC) accounts for approximately 10-15% of all lung cancers. The prognosis is poor with median survival in the advanced stage remaining at around 12 months. Despite applying every known therapeutic approach, no major breakthrough has improved the overall survival in the last 30 years. Historically, experiments performed on conventional cell lines may have limitations of not accurately reflecting the complex biological and genomic heterogeneity of this disease. However, additional knowledge gained from recently developed genetically engineered mouse models (GEMMs) and patient derived xenografts (PDXs) have made encouraging inroads. Whole genome sequencing (WGS) data reveals a high mutational burden and a number of genetic alterations but low frequency of targetable mutations. Despite several failures, considerable therapeutic opportunities have recently emerged. Potentially promising therapies include those targeting DNA damage repair, stem cell/renewal and drug resistant mechanisms. Modest success has also been achieved with immune checkpoint inhibitors while therapeutic exploration of various other components of the immune system is underway. However, the complex heterogeneities reflect the need for accurate bio-markers to translate novel discoveries into clinical benefit. Additionally, the molecular mechanisms that differentiate chemo-sensitive from chemo-refractory disease remain unknown. Obtaining reliable tumour samples by utilising novel techniques such as endobronchial ultrasound guided needle aspiration or adopting to liquid biopsies are becoming popular. This review will focus on recent technological and therapeutic advancements to surmount this recalcitrant disease.
| S-EPMC6826371 | biostudies-literature
Project description:Maintenance therapy is a treatment strategy that can prolong survival in patients with advanced non-small cell lung cancer (NSCLC). The increased survival achieved with maintenance therapy has led to new treatment options that should be chosen in accordance with the preferences of patients and physicians. Personalized maintenance therapy involves identification of histological subtypes and molecular features of tumors, thereby improving treatment outcomes. Many clinical trials have been conducted to establish new treatment strategies for patients with advanced NSCLC with non-squamous cell histology. The discovery of epidermal growth factor receptor (EGFR) mutations was the most significant innovation for personalized therapy in NSCLC patients. First generation EGFR-tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have significantly contributed to greatly increased survival in specific patients harboring activating EGFR mutations such as exon 19 deletion and L858R point mutation. Based on clinical trials of different maintenance therapy strategies, we identified the regimen is the most promising and highlighted for patients whom should be given specific kinds of therapy now and in future studies.
| S-EPMC4367627 | biostudies-other
Project description:The recognition that non-small cell lung cancer (NSCLC) is not a single disease entity, but rather a collection of distinct molecularly driven neoplasms, has permanently shifted the therapeutic landscape of NSCLC to a personalized approach. This personalization of NSCLC therapy is typified by the dramatic response rates seen in EGFR mutant NSCLC when treated with targeted tyrosine kinase inhibitor therapy and in ALK translocation-driven NSCLC when treated with ALK inhibitors. Targeted therapeutic approaches in NSCLC necessitate consideration of more invasive biopsy techniques aimed at providing sufficient tissue for both histological determination and molecular profiling in all patients with stage IV disease both at the time of diagnosis and at the time of disease progression. Comprehensive genotyping efforts have identified oncogenic drivers in 62% lung adenocarcinomas and an increasing proportion of squamous cell carcinomas of the lung. The identification of these oncogenic drivers and the triage of patients to clinical trials evaluating novel targeted therapeutic approaches will increasingly mold a landscape of personalized lung cancer therapy where each genotype has an associated targeted therapy. This review outlines the state of personalized lung cancer therapy as it pertains to individual NSCLC genotypes.
| S-EPMC4836173 | biostudies-literature
Project description:Despite some recent advances in the management of advanced non-small cell lung cancer (NSCLC), prognosis for these patients remains poor. Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have however provided a new therapeutic option in this disease setting and EGFR mutation testing is now routine practice for newly diagnosed NSCLC patients. A proportion of patients will not respond to first-generation EGFR-TKIs however, and those who do will ultimately develop resistance and disease relapse. Next-generation EGFR-TKIs which inhibit multiple members of the EGFR family are being developed in order to increase sensitivity and overcome resistance to existing agents. Afatinib (BIBW 2992) is an oral, irreversible inhibitor of EGFR and HER2 tyrosine kinases and is the most advanced of these agents in clinical development. Pre-clinical and early-phase clinical trials have demonstrated a favorable safety profile as a single agent and in combination with other anti-cancer agents, and provide evidence of clinical activity in advanced NSCLC. The LUX-Lung trials suggest that for selected patients, afatinib offers symptomatic improvement and prolonged progression-free survival, although this has not yet translated into improved overall survival. This article aims to review the use of EGFR-TKIs in the management of advanced NSCLC and the mechanisms underlying resistance to these agents. We will discuss the current pre-clinical and clinical data regarding afatinib, its potential to overcome resistance to first-generation TKIs, and its emerging role in advanced NSCLC treatment.
| S-EPMC5312479 | biostudies-literature
Project description:Lung cancer is the leading cause of cancer-related mortality in the United States. Over the past 40 years, treatments with standard chemotherapy agents have not resulted in substantial improvements in long-term survival for patients with advanced lung cancer. Therefore, new targets have been sought, and angiogenesis is a promising target for non-small cell lung cancer (NSCLC). Bevacizumab, a monoclonal antibody targeted against the vascular endothelial growth factor, is the only antiangiogenic agent currently recommended by NCCN for the treatment of advanced NSCLC. However, several antibody-based therapies and multitargeted tyrosine kinase inhibitors are currently under investigation for the treatment of patients with NSCLC. This article summarizes the available clinical trial data on the efficacy and safety of these agents in patients with advanced lung cancer.
| S-EPMC6628716 | biostudies-literature
Project description:IntroductionPD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.MethodsWe analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.ResultsIrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001).ConclusionsApproximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.
| S-EPMC8277237 | biostudies-literature