No abstract available.
Animals ; Asian Continental Ancestry Group* ; CHO Cells ; Cricetinae ; Cricetulus* ; Female ; Hepatitis B Surface Antigens* ; Hepatitis B Vaccines ; Humans ; Ovary*

Background: The kinetics of neutralizing antibodies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) play an important role in evaluating vaccine efficacy and durability, herd immunity, additional vaccination, and prediction models of immune protection against coronavirus disease 2019. Materials and Methods: Serum collection times were 4 and 8 weeks after 1st inoculation of AZD1222 (AstraZeneca, Cambridge, UK), and 2 and 16 weeks after 2nd inoculation with 12-week dosing intervals. Neutralizing antibody (Nab) titers were measured indirectly using commercially available R-FIND SARS-CoV-2 Neutralizing Antibody ELISA Kit (SG Medical Inc., Seoul, Korea). Possible influences of gender, age, and adverse events on neutralizing antibody titer were also investigated. Results: Nab titers (median inhibition %) started to decrease shortly after reaching peaks.This decrease was more pronounced in the elderly group (≥56 years) than in the young group (≤39 years) at 8 weeks (49.5% vs. 55.4%, P = 0.021) and 16 weeks (40.6% vs. 53.9%, P = 0.006) after the 1st and 2nd inoculation. And Nab titers were inversely correlated with age in the 8-week (r = -0.2091, P = 0.0284) and the 28-week group (r = -0.2811, P = 0.0029). Seropositive conversion of Nab reached 89.1% and 100% following 1st and 2nd inoculation. This 100% seropositivity was dropped sharply to 74.5% after 16 weeks. Compared to subjects without adverse events (51.8%), median inhibition was higher in subjects with one or more systemic adverse events (74.2%, P = 0.0203) or those with one or more local and systemic adverse events (77.1%, P = 0.0003). Conclusion Nab induced by AZD1222 (AstraZeneca, UK) vaccination started to degrade shortly after the production period. Nab titers were lower in the elderly than in younger group during the degradation period. This seems to be because the degradation process of Nab is more pronounced in the elderly. This may explain why the frequency of breakthrough infections, disease severity, and mortality were higher in the elderly and may require revaccination to ensure robust immunity.

Background: High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites. Methods: Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method. Results: During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively. Conclusions Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.

CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress CD4+ T cells, ameliorating autoimmune diseases, whereas it induces activation of CD8+ T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased CD11b+Gr-1+ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both CD8+ T cells and CD4+ T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce CD11b+Gr-1+ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.
Autoimmune Diseases ; Immunosuppression ; Myeloid Cells ; T-Lymphocytes

PURPOSE: In this study, we evaluated the effects of training for survival prediction of terminally ill patients in terms of medical professionals' confidence, accuracy and knowledge of survival prediction. METHODS: Twenty-nine participants completed a self-administered questionnaire where they scored their confidence, accuracy and knowledge of survival prediction before and after the training session. The training was provided in July 2009 at a university hospital located in Gyeonggi province, Republic of Korea. The participants were instructed by a professor of family medicine specialized in hospice palliative medicine to predict survival of a case using the palliative prognostic score and objective prognostic score. The training was provided in the form of a PowerPoint presentation for 40 minutes. RESULTS: Participants' confidence in survival prediction significantly increased from 4.00+/-1.73 (mean+/-SD) (0~10, visual analogue scale) to 5.83+/-1.71 after the training (P<0.001). Before training, participant's level of confidence significantly correlated with their age (P=0.04). The training significantly improved the correlation between the confidence level and the number of terminal cancer patients whom they have experienced (P=0.005 before training, P=0.017 after training). Participant's accuracy in survival prediction also significantly improved from 14 of 29 (48%) to 27 of 29 (93.1%) (P<0.001). The change in knowledge of survival prediction was too small to be statistically analyzed. CONCLUSION: After training, the confidence and accuracy scores significantly improved. Further study with a greater number of participants is needed to generalize this finding.
Hospices ; Humans ; Palliative Care ; Prognosis ; Republic of Korea ; Terminally Ill ; Surveys and Questionnaires

Chronic virus infection leads to the functional impairment of dendritic cells (DCs) as well as T cells, limiting the clinical usefulness of DC-based therapeutic vaccine against chronic virus infection. Meanwhile, B cells have been known to maintain the ability to differentiate plasma cells producing antibodies even during chronic virus infection. Previously, alpha-galactosylceramide (alphaGC) and cognate peptide-loaded B cells were comparable to DCs in priming peptide-specific CD8+ T cells as antigen presenting cells (APCs). Here, we investigated whether B cells activated by alphaGC can improve virus-specific T cell immune responses instead of DCs during chronic virus infection. We found that comparable to B cells isolated from naive mice, chronic B cells isolated from chronically infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) after alphaGC-loading could activate CD1d-restricted invariant natural killer T (iNKT) cells to produce effector cytokines and upregulate co-stimulatory molecules in both naive and chronically infected mice. Similar to naive B cells, chronic B cells efficiently primed LCMV glycoprotein (GP) 33-41-specific P14 CD8+ T cells in vivo, thereby allowing the proliferation of functional CD8+ T cells. Importantly, when alphaGC and cognate epitope-loaded chronic B cells were transferred into chronically infected mice, the mice showed a significant increase in the population of epitope-specific CD8+ T cells and the accelerated control of viremia. Therefore, our studies demonstrate that reciprocal activation between alphaGC-loaded chronic B cells and iNKT cells can strengthen virus-specific T cell immune responses, providing an effective regimen of autologous B cell-based therapeutic vaccine to treat chronic virus infection.
Animals ; Antibodies ; Antigen-Presenting Cells ; B-Lymphocytes ; Clone Cells ; Cytokines ; Dendritic Cells ; Glycoproteins ; Lymphocytic choriomeningitis virus ; Mice ; Natural Killer T-Cells ; Plasma Cells ; T-Lymphocytes ; Viremia

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

BACKGROUND: Human papillomavirus (HPV) infection is responsible for cervical cancer, a common cancer in women. Since HPV infection and cancer development are controlled by the host immune system, immunotherapy against HPV can be helpful in preventing or treating HPV-associated cervical cancer. Two oncoproteins of HPV16, E6 and E7, are promising targets for immunotherapy against cervical cancer, because they are constitutively expressed in cervical cancer. METHODS: Since cellular vaccines using B cells as well as dendritic cells offer an efficient approach to cancer immunotherapy, we opted to use B cells. We evaluated the immunogenicity and anti-tumor effects of a B cell vaccine transduced with HPV16 E6/E7-expressing adenovirus. RESULTS: Vaccination with HPV16 E6/E7-transduced B cells induced E6/E7-specific CD8+ T cell-dependent immune responses and generated anti-tumor effects against E6/E7-expressing TC-1 tumor. The anti-tumor effect induced by this B cell vaccine was similar to that elicited by DC vaccine, showing that B cells can be used as an alternative to dendritic cells for cellular vaccines. CONCLUSION: Thisstudy has shown the feasibility of using B cells as immunogenic APCs and the potential for developing prophylactic and therapeutic vaccines against HPV-associated cervical cancer using a B cell vaccine transduced with adenovirus expressing HPV16 E6/E7.
Adenoviridae ; B-Lymphocytes* ; Dendritic Cells ; Female ; Humans ; Immune System ; Immunotherapy ; Oncogene Proteins ; Uterine Cervical Neoplasms ; Vaccination ; Vaccines

Purpose: BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer. Materials and Methods: Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses. Results: Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients. Conclusion BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.