scholarly journals Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yvette Robbins ◽  
Sarah Greene ◽  
Jay Friedman ◽  
Paul E Clavijo ◽  
Carter Van Waes ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Growth Inhibition ◽  
Nk Cells ◽  
Head And Neck ◽  
Neck Cancer ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Myeloid Cells ◽  
Tumor Rejection ◽  
Tumor Control

Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1-dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. The clinical study of PD-L1 CAR haNKs is warranted.

scholarly journals Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells

2020 ◽  
Author(s):  
Yvette Robbins ◽  
Sarah Greene ◽  
Jay Friedman ◽  
Paul E. Clavijo ◽  
Carter Van Waes ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Growth Inhibition ◽  
Nk Cells ◽  
Head And Neck ◽  
Neck Cancer ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Myeloid Cells ◽  
Tumor Rejection ◽  
Tumor Control

AbstractFailed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1 dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. The clinical study of PD-L1 CAR haNKs is warranted.

scholarly journals Automated Non-Coplanar VMAT for Dose Escalation in Recurrent Head and Neck Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1910
Author(s):  
Kaley Woods ◽  
Robert K. Chin ◽  
Kiri A. Cook ◽  
Ke Sheng ◽  
Amar U. Kishan ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Dose Escalation ◽  
Volumetric Modulated Arc Therapy ◽  
Normal Tissue Complication Probability ◽  
Tumor Control ◽  
Tumor Control Probability ◽  
Increased Risk ◽  
Recurrent Head

This study evaluates the potential for tumor dose escalation in recurrent head and neck cancer (rHNC) patients with automated non-coplanar volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) planning (HyperArc). Twenty rHNC patients are planned with conventional VMAT SBRT to 40 Gy while minimizing organ-at-risk (OAR) doses. They are then re-planned with the HyperArc technique to match these minimal OAR doses while escalating the target dose as high as possible. Then, we compare the dosimetry, tumor control probability (TCP), and normal tissue complication probability (NTCP) for the two plan types. Our results show that the HyperArc technique significantly increases the mean planning target volume (PTV) and gross tumor volume (GTV) doses by 10.8 ± 4.4 Gy (25%) and 11.5 ± 5.1 Gy (26%) on average, respectively. There are no clinically significant differences in OAR doses, with maximum dose differences of <2 Gy on average. The average TCP is 23% (± 21%) higher for HyperArc than conventional plans, with no significant differences in NTCP for the brainstem, cord, mandible, or larynx. HyperArc can achieve significant tumor dose escalation while maintaining minimal OAR doses in the head and neck—potentially enabling improved local control for rHNC SBRT patients without increased risk of treatment-related toxicities.

scholarly journals Decreased NK Cells in Patients with Head and Neck Cancer Determined in Archival DNA

2012 ◽  
Vol 18 (22) ◽  
pp. 6147-6154 ◽  
Author(s):  
William P. Accomando ◽  
John K. Wiencke ◽  
E. Andres Houseman ◽  
Rondi A. Butler ◽  
Shichun Zheng ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Nk Cells ◽  
Head And Neck ◽  
Neck Cancer ◽  
Archival Dna

scholarly journals Adaptive radiotherapy for head and neck cancer

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Enis Tinjak ◽  
Velda Smajlbegović ◽  
Adnan Beganović ◽  
Mirjana Ristanić ◽  
Halil Ćorović ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Adaptive Radiotherapy ◽  
Tumor Control ◽  
Parotid Glands ◽  
Image Guided Radiotherapy ◽  
The Impact

Introduction: Radiation therapy has long played an integral role in the manage¬ment of locally advanced head and neck cancer (HNC), both for organ preservation and to improve tumor control in the postoperative setting. The aim of this research is to investigate the effects of adaptive radiotherapy on dosimetric, clinical, and toxicity outcomes for patients with head and neck cancer undergoing radiation therapy treatment. Many sources have reported volume reductions in the primary target, nodal volumes, and parotid glands over treatment, which may result in unintended dosimetric changes affecting the side effect profile and even efficacy of the treatment. Adaptive radiotherapy (ART) is an interesting treatment paradigm that has been developed to directly adjust to these changes.Material and methods: This research contains the results of 15 studies, including clinical trials, randomized prospective and retrospective studies. The researches analyze the impact of radiation therapy on changes in tumor volume and the relationship with planned radiation dose delivery, as well as the possibility of using adaptive radiotherapy in response to identified changes. Also, medical articles and abstracts that are closely related to the title of adaptive radiotherapy were researched.Results: The application of ART significantly improved the quality of life of patients with head and neck cancer, as well as two-year locoregional control of the disease. The average time to apply ART is the middle of the treatment course approximately 17 to 20 fractions of the treatment.Conclusion: Based on systematic review of the literature, evidence based changes in target volumes and dose reduction at OAR, adaptive radiotherapy is recommended treatment for most of the patients with head and neck cancer with the support of image-guided radiotherapy.

Critical Impact of Radiotherapy Protocol Compliance and Quality in the Treatment of Advanced Head and Neck Cancer: Results From TROG 02.02

2010 ◽  
Vol 28 (18) ◽  
pp. 2996-3001 ◽  
Author(s):  
Lester J. Peters ◽  
Brian O'Sullivan ◽  
Jordi Giralt ◽  
Thomas J. Fitzgerald ◽  
Andy Trotti ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Phase Iii ◽  
Treatment Center ◽  
Tumor Control ◽  
Advanced Head ◽  
Number Of Patients ◽  
Protocol Compliance ◽  
The Impact

Purpose To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer. Patients and Methods The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality. Results At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; ≥ 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): −2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively. Conclusion These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.

Sign in / Sign up

Export Citation Format

Share Document