ABSTRACT
Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the prevalence and epidemiologic characteristics of seronegative spondyloarthritis (SpAs) in Chinese army force in different areas.</p><p><b>METHODS</b>4-phase survey was conducted in 21 750 Chinese army, including: face-to-face interviews with standardized COPCORD questionnaires (Phase I screening); further examination on the suspected cases; identification of inflammatory joint and spinal diseases (Phase II); identification of SpAs (AS and uSpA) by more than two experienced specialists in rheumatology; further examination with X-rays and laboratory detection of HLA-B27 (Phase III); and data analysis (Phase IV).</p><p><b>RESULTS</b>Among 21 750 army men, 21 cases of RA, 106 cases of SpAs were identified, with prevalence rates of 0.966 per thousand, 4.87 per thousand respectively. In 106 cases of SpAs, there were 46 cases of ankylosing spondylitis (AS), 52 cases of undifferentiated SpAs (uSpAs) with the prevalence rates of 2.11 per thousand and 2.39 per thousand respectively. Few cases of reactive arthritis (ReA) and Reiter's syndrome (RS) were identified (6 and 1 cases respectively). The prevalence of AS, uSpAs were higher in navy than that in the ground force or the air force. Soldiers in cold and damp areas had higher prevalence rates than that in the plain and drought areas.</p><p><b>CONCLUSION</b>The prevalence of SpA (especially AS and uSpA) in Chinese army force was similar to that in the civilians. SpA (AS and uSpA) was more prevalent seen in the Navy. The incidence of SpA (AS and uSpA) was influenced by environmental factors such as coldness and dampness.</p>