Immunotherapy for non-small cell lung cancer: current concepts and clinical trials

Mayor, Marissa; Yang, Neng; Sterman, Daniel H.; Jones, David R.; Adusumilli, Prasad S.

doi:10.1093/ejcts/ezv371

Cited by 38 publications

(31 citation statements)

References 77 publications

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“…Treatment with nivolumab also resulted in an OS rate of 42% (95% confidence interval [CI] 33–50) at 1 year, 24% (95% CI 17–33) at 2 years, and 18% (95% CI 11–25) at 3 years; similar results have been reported for the nonsquamous and squamous histological subtypes 35. In another Phase I study that included 122 patients with NSCLC, nivolumab was administered once every 2 weeks at doses of 0.1–10 mg/kg.…”

Section: Efficacy and Safety Of Immunotherapy For Nsclcsupporting

confidence: 73%

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Potential role of immunotherapy in advanced non-small-cell lung cancer

Mello

Veloso

Catarina

et al. 2016

OTT

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Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework.

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Section: Efficacy and Safety Of Immunotherapy For Nsclcsupporting

confidence: 73%

“…This mAb has shown anticancer activity against several tumor types including NSCLC 35. The first Phase I clinical trial of an anti-PD-1 antibody showed activity in NSCLC, and subsequent studies have demonstrated that a PD-1 pathway blockade supports durable tumor responses 36.…”

Section: Efficacy and Safety Of Immunotherapy For Nsclcmentioning

confidence: 99%

Potential role of immunotherapy in advanced non-small-cell lung cancer

Mello

Veloso

Catarina

et al. 2016

OTT

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“…Adoptive transfer of tumor-targeted T cells may thus fill the void in patients with less immunogenic or "noninflamed" tumors. As adoptively transferred T cells are themselves susceptible to immunoinhibition, strategies that combine adoptive T cell therapy with checkpoint antibody blockade have been investigated using mouse T cells (27)(28)(29). Antibody-mediated checkpoint blockade effectively provides reversal of immunoinhibition in a systemic fashion that may result in auto-Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells.…”

Section: Introductionmentioning

confidence: 99%

Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition

Cherkassky¹,

Morello²,

Villena-Vargas³

et al. 2016

Journal of Clinical Investigation

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854

688

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Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells. This adaptive resistance compromises the efficacy of chimeric antigen receptor (CAR) T cell therapies, which redirect T cells to solid tumors. Here, we investigated whether programmed death-1-mediated (PD-1-mediated) T cell exhaustion affects mesothelin-targeted CAR T cells and explored cell-intrinsic strategies to overcome inhibition of CAR T cells. Using an orthotopic mouse model of pleural mesothelioma, we determined that relatively high doses of both CD28- and 4-1BB-based second-generation CAR T cells achieved tumor eradication. CAR-mediated CD28 and 4-1BB costimulation resulted in similar levels of T cell persistence in animals treated with low T cell doses; however, PD-1 upregulation within the tumor microenvironment inhibited T cell function. At lower doses, 4-1BB CAR T cells retained their cytotoxic and cytokine secretion functions longer than CD28 CAR T cells. The prolonged function of 4-1BB CAR T cells correlated with improved survival. PD-1/PD-1 ligand [PD-L1] pathway interference, through PD-1 antibody checkpoint blockade, cell-intrinsic PD-1 shRNA blockade, or a PD-1 dominant negative receptor, restored the effector function of CD28 CAR T cells. These findings provide mechanistic insights into human CAR T cell exhaustion in solid tumors and suggest that PD-1/PD-L1 blockade may be an effective strategy for improving the potency of CAR T cell therapies.

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“…pD-1 belongs to the CD28 family of proteins. It is a receptor located on the surface of T cells to regulate their proliferation and activation [18]. Its ligand is programmed cell death-ligand 1 (pD-L1), a 40-kDa type 1 transmembrane protein.…”

Section: Immune Checkpoint Inhibitormentioning

confidence: 99%

A new hope: the immunotherapy in small cell lung cancer

Li¹,

Yuan²,

Ma³

et al. 2016

neo

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Small cell lung cancer (SCLC) is of a high-grade malignancy with a high metastatic potential and poor clinical prognosis. Unfortunately, SCLC initially exhibits a good response to chemotherapy and radiation therapy, but inevitably, relapses decrease patients' chance of survival. Despite tremendous advances on the development of new chemotherapeutic agents, the prognosis of this disease remains poor. Immunotherapy plays a role in eliciting an anticancer response by modulating the patient's immune response of the tumor. Several studies have demonstrated that abnormal autoimmune regulation has a close relationship with SCLC. Thus, several immunotherapy trials are focused on SCLC treatment, including such approaches as immune checkpoints blockers, tumor vaccine, antigenic targets and adoptive cellular immunotherapy to benefit patients with SCLC. To date, the results from immunotherapy in SCLC have not been promising. For example, tumor vaccines have not been demonstrated to have a significant survival benefit. However, there have been many promising advances with immune checkpoints blockers. This review will provide a general overview of immunotherapy in SCLC. The landmark clinical trials in previous successful immunotherapy studies are summarized here. Finally, the challenges of immunotherapy in SCLC are discussed to facilitate the prediction of possible and valuable strategies for future therapy.

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Immunotherapy for non-small cell lung cancer: current concepts and clinical trials

Cited by 38 publications

References 77 publications

Potential role of immunotherapy in advanced non-small-cell lung cancer

Potential role of immunotherapy in advanced non-small-cell lung cancer

Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition

A new hope: the immunotherapy in small cell lung cancer

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