scholarly journals Case Report: In Situ Vaccination by Autologous CD16+ Dendritic Cells and Anti-PD-L 1 Antibody Synergized With Radiotherapy To Boost T Cells-Mediated Antitumor Efficacy In A Psoriatic Patient With Cutaneous Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun-Wei Huang ◽  
Chun-Lin Kuo ◽  
Li-Tzu Wang ◽  
Kevin Sheng-Kai Ma ◽  
Wen-Yen Huang ◽  
...  

The combination of radiotherapy and immunotherapy improves the survival rate of patients with malignancies developed through escape from T-cell-mediated immune surveillance. Immune checkpoint inhibitors, such as anti-programmed cell death protein-ligand 1 (anti-PD-L1) antibody, are used to rescue exhausted T cells. Simultaneously, dendritic cells (DCs) which are antigen-presenting cells that can initiate T-cell activation, are used to induce a tumor-specific immune response. However, the synergistic antitumor efficacy of the aforementioned combinational immunotherapy with intratumoral injection of low-dose DCs has not been reported, and the underlying therapeutic mechanism requires further investigation. Herein, we present the special case of a psoriatic patient with cutaneous squamous cell carcinoma (cSCC) in the right inguinal region, these two diseases characterized by opposing contradiction, further complicating treatments and side-effect management efforts. To treat the intractable SCC without exaggerating psoriasis, we developed the triple-regimen therapy (TRT) with the intratumoral injection of low-dose autologous DCs and anti-PD-L1 combined with radiotherapy. The injected DCs were obtained simply through leukapheresis without prior G-CSF administration for mobilization nor tumor-antigen loading for expansion. The patient received three radiation doses (24, 18, and 18 Gy) combined with three intratumoral injections of anti-PD-L1 antibody (40, 60, and 120 mg) plus autologous DCs (80% of the DC subpopulation being CD16+ myeloid DC with approximate amounts of 7.3 × 104, 2.5 × 106, and 1.7 × 107) within 10 weeks. The efficacy of the TRT was encouraging in shrinking tumor mass with remarkable SUVmax reduction (approximately 42%) on FDG PET-Scan despite relatively low-dose DCs were available. The low-dose intratumoral immunotherapy induced mild cutaneous side effects as expected. The transcriptomes were compared between pre-TRT and post-TRT biopsies to analyze underlying mechanical pathways of the TRT protocol. Over 10 highly significantly enriched T-cell-related pathways (P <0.0001) were identified in post-TRT biopsies. In addition, the activation of both innate and adaptive immunity was significantly enriched in post-TRT peripheral blood samples. We develop the easily accessible TRT which produces both local anti-tumor T-cell responses and systemic antitumor immunity for treating cSCC patients, especially for those with autoimmune disease.

2009 ◽  
Vol 129 (10) ◽  
pp. 2451-2462 ◽  
Author(s):  
Mark J. Bluth ◽  
Lisa C. Zaba ◽  
Dariush Moussai ◽  
Mayte Suárez-Fariñas ◽  
Helen Kaporis ◽  
...  

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A504-A504
Author(s):  
Thomas Davis ◽  
Arthur DeCillis ◽  
Richard Hernandez ◽  
Jessica Price ◽  
Craig Carey ◽  
...  

BackgroundGEN-011 is a personalized neoantigen-targeted peripheral blood T cell therapy (NPT) developed for the treatment of adult patients (pts) with solid tumors. The proprietary ATLAS™ (Antigen Lead Acquisition System) will be used to identify true immunogenic neoantigens from each patient‘s tumor mutanome that are recognized by their own CD4+ and/or CD8+ T cells. ATLAS will also identify Inhibigens™, antigen targets of T cells that promote tumor growth.1 Autologous peripheral T cells will be specifically stimulated by up to 30 ATLAS-identified neoantigens, avoiding Inhibigens, to generate an adoptive T cell product. Preliminary data show yields of billions of highly active T cells with 96% neoantigen targeting across 89% of ATLAS selected neoantigens.MethodsTITAN-1 is a multicenter Phase 1 study of GEN-011 NPTs in patients with refractory melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), renal cell carcinoma (RCC), small cell lung cancer (SCLC), cutaneous squamous cell carcinoma (CSCC), and anal squamous cell carcinoma (ASCC). Patients may enter into one of 2 cohorts of 6 DLT-evaluable patients, either a multiple lower dose (MLD) regimen of GEN-011 as an IV infusion at 4-week intervals, up to 5 doses maximum without lymphodepletion, or a single high dose (SHD) regimen of GEN-011 after flu/cy lymphodepletion. Each dose of GEN-011 will be followed by a course of interleukin-2 (IL-2). Patients will be followed for safety, immunogenicity, and anti-tumor activity over approximately a 5-month treatment period. A long-term follow-up will continue through 2 years after the initial dose of GEN-011.Trial Registration clinicaltrials.gov identifier: NCT04596033ReferencesLam H, et al. An empirical antigen selection method identifies neoantigens that either elicit broad anti-tumor response or drive tumor growth. Cancer Discovery 2021 March; 11(3):696–713.Ethics ApprovalThis study was approved by Western Institutional Review Board, approval number 1-1078861-1


2005 ◽  
Vol 55 (2) ◽  
pp. 151-159 ◽  
Author(s):  
Koichi Sakakura ◽  
Kazuaki Chikamatsu ◽  
Katsumasa Takahashi ◽  
Theresa L. Whiteside ◽  
Nobuhiko Furuya

2019 ◽  
Vol 139 (5) ◽  
pp. S128
Author(s):  
M.J. Whitley ◽  
C. Lai ◽  
J. Suwanpradid ◽  
R.R. Rudolph ◽  
D. Zelac ◽  
...  

Head & Neck ◽  
2020 ◽  
Vol 42 (11) ◽  
pp. 3226-3234
Author(s):  
Stefan Kraft ◽  
Shekhar K. Gadkaree ◽  
Daniel G. Deschler ◽  
Derrick T. Lin ◽  
Mai P. Hoang ◽  
...  

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