Day 1 :
Keynote Forum
Leung KN
School of Life Sciences, The Chinese University of Hong Kong, China
Keynote: Immunomodulatory and Anti-tumor Activities of Conjugated Linolenic Acids
Time : 10:00-10:30
Biography:
Prof. K.N. Leung received his B.Sc. Degree in Biochemistry from The Chinese University of Hong Kong (CUHK) and obtained the Ph.D. Degree in Microbiology and Immunology from The Australian National University. After two years of postdoctoral work at the Pathology Department of the University of Cambridge, he returned to the CUHK as a Lecturer in the Department of Biochemistry in 1983. Prof. Leung was the former Dean of General Education in Chung Chi College, the Associate Dean of Science (Education) of CUHK and the Chairman of the Hong Kong Society for Immunology. He is now an Adjunct Professor in the School of Life Sciences, CUHK and the School of Science and Engineering, CUHK (Shenzhen). His main research interests include immunopharmacological studies of natural products and Chinese medicinal herbs; cancer immunotherapy; nutrition, immunity and cancer.
Abstract:
Conjugated linolenic acids (CLN) refer to a group of positional and geometrical conjugated trienoic isomers of linolenic acid (C18:3), which can be isolated from various plant seed oils. Recent studies have shown that CLN isomers possess diverse biological and pharmacological activities, including anti-inflammatory, antioxidative, hypolipidemic, and anti-tumor properties. However, their immunomodulatory activities on macrophages and anti-tumor action mechanisms on human myeloid cells remain poorly understood. In this study, jacaric acid (8Z, 10E, 12Z-octadecatrienoic acid), a CLN isomer that is present in jacaranda seed oil, was found to inhibit the in vitro and in vivo growth of human eosinophilic leukemia EoL-1 cells, while exhibiting no significant cytotoxicity to normal murine cells. Mechanistic studies showed that jacaric acid triggered cell cycle arrest at G0/G1 phase and induced apoptotic events in EoL-1 cells, including DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization. Moreover, jacaric acid-treated EoL-1 cells also underwent eosinophilic differentiation as determined by morphological and phenotypic criteria. Interestingly, jacaric acid exhibited no significant cytotoxicity on the thioglycollate-induced peritoneal macrophages but stimulated their cytostatic activity towards tumor cells, and increased their endocytic ability and production of nitric oxide and several pro-inflammatory cytokines such as IFN-g, IL-1β and TNF-a in vitro. Collectively, our results indicate that jacaric acid can activate murine macrophages and exerts its direct anti-tumor effects on human myeloid leukemia cells via induction of apoptosis and differentiation of the leukemia cells. Therefore, jacaric acid might be a potential candidate for the treatment of some forms of myeloid leukemia.
Keynote Forum
Jennifer Wu
Hollings Cancer Center-Medical University of South Carolina, USA
Keynote: Beyond immune checkpoint: Targeting soluble NKG2D ligands for cancer immunotherapy
Time : 10:30-11:00
Biography:
Jennifer Wu has received her PhD from the University of British Columbia and Post doctorate training at the Fred Hutchinson Cancer Research Center. She has joined the Faculty of Medicine at the University of Washington and tenured as an Associate Professor. In 2011, she has accepted the faculty appointment at the Medical University of South Carolina and became a Member of Hollings Cancer Center Cancer Immunology Program. Her research focuses on understanding how cancer cells disable the immune system with the ultimate goal to develop effective immunotherapy of cancer. Her work was the first to shown that tumors shed NKG2D ligand sMIC to perturb the maintenance of tumor-killing NK cells and to facilitate tumor metastasis. Her research team is the first to demonstrate that antibody targeting sMIC refuels and revamps endogenous innate and adoptive anti-tumor responses. Her findings were extensively published in Nature, Journal of Clinical investigations, Clinical Cancer Research, Oncoimmunology. She has served as the elected Committee Chair of Cancer in the Federation of Clinical Immunology Society and Editorial Board of many cancer immunology related Journals.
Abstract:
In response to oncogenic insult, human cells were induced to express a family of MHC I-chain related molecules A and B (MICA and MICB, generally termed MIC) on the surface which serve as the ligands for the activating immune receptor NKG2D expressed by all human NK, CD8 T, NKT, and subsets of gd T cells. Theoretically, engagement of NKG2D by tumor cell surface MIC is deemed to signal and provoke the immune system to eliminate transformed cells. Clinically, almost all advanced tumors in cancer patients produce soluble MIC through proteolytic shedding mediated by metalloproteases or by release in exosomes derived from the cell membrane. Tumor-derived sMIC is known to be highly immune suppressive and profoundly insults the immune system by down regulating receptor NKG2D expression on effector NK and T cells, driving the expansion of tumor favoring myeloid suppression cells, skewing macrophages into alternatively activated phenotypes and perturbing NK cell peripheral maintenance. High levels of serum sMIC significantly correlate with advanced diseases of many types of cancer. These observations clearly endorse sMIC to be a cancer immune therapeutic target. However, due to mice lack homologues to human MIC, this concept was not proven until our recent studies. Using a “humanized” MIC-transgenic spontaneous mouse model which recapitulates the NKG2D-mediated onco-immune dynamics of human cancer patients, we show that neutralizing circulating sMIC with a non-blocking antibody that does not block the interaction of MIC with NKG2D revamps endogenous innate and antigen-specific CD8 T cell responses. We show that therapy with the non-blocking sMIC-neutralizing antibody effectively debulked primary tumor and eliminated metastasis. Clearing sMIC with the neutralizing antibody also enhanced the efficacy of other cancer immunotherapeutic modalities, such as immune checkpoint blockade or cell-based therapy preclinically. Our study has launched a new avenue of cancer immunotherapy which can be readily translated into clinical trials.
Keynote Forum
Liang Xu
University of Kansas Cancer Center, USA
Keynote: Antibody based immunotherapy targeting pancreatic cancer stem cells
Time : 10:20-11:50
Biography:
Liang Xu has obtained his MD and PhD in Gastroenterology at the Fourth Military Medical University of China in 1992 and did Post-doc research on Molecular Biology at University of Louvain, Belgium, 1994, then at Stanford University, 1996. He has then moved to the Georgetown University and developed a novel non-viral tumor targeted delivery system for cancer therapy, which is in Phase II clinical trials. In 2002, he joined the Faculty at University of Michigan to discover the novel small molecule inhibitors of anti-apoptotic proteins. He is a Co-Inventor of the first Bcl-2 inhibitor that entered into clinical trials. In 2010, he has obtained a Rising Star Award and became an Associate Professor with Tenure at University of Kansas Cancer Center. He has more than 25 patents with four INDs in advanced clinical trials. He is currently a Professor of Cancer Biology at University of Kansas and has been funded by NIH, DOD and Komen Foundation. He is working on cancer drug discovery and immunotherapy targeting cancer stem cells.
Abstract:
CD44s is a surface marker of cancer stem cells (CSCs); high tumor levels correlate with metastasis and recurrence as well as poor outcomes of patients. Monoclonal antibodies against CD44s might eliminate CSCs with minimal toxicity. This strategy is unclear for treatment of pancreatic cancer and little is known about how anti-CD44s affect pancreatic cancer initiation or recurrence after radiotherapy. We measured CD44s levels in tissue samples and pancreatic cancer cell lines by immunohistochemistry, real-time PCR and immunoblot; levels were correlated with patient survival times. We studied the effects of anti-CD44s in mice with human pancreatic tumor xenografts and used flow cytometry to determine effects on TICs. Changes in CD44s signaling were examined by real-time PCR, immunoblot, reporter assay and in vitro tumorsphere formation assays. The levels of CD44s were significantly higher in pancreatic cancer than adjacent non-tumor tissues. Patients whose tumors expressed high levels of CD44s had a median survival of 10 months, compared to 43 months for those with low levels. Anti-CD44s reduced the growth, metastasis and post-radiation recurrence of pancreatic xenograft tumors in mice. The antibody reduced the number of CSCs in cultured pancreatic cancer cells and in xenografts as well as their tumorigenicity. Anti-CD44s down-regulated the stem cell self-renewal genes Nanog, Sox-2, and Rex-1, and inhibited the STAT3-mediated cell proliferation and survival signaling. The CSC marker CD44s is up-regulated in human pancreatic tumors and associated with patient survival time. CD44s is required for initiation, growth, metastasis and post-radiation recurrence of xenograft tumors in mice. Anti-CD44s eliminated bulk tumor cells as well as CSCs from the tumors. Immunotherapy targeting CD44s might be developed to block pancreatic cancer progression and post-radiotherapy recurrence in patients.
- Workshop / Special Session
Location: Melbourne, Australia
Session Introduction
Weidong Han
Professor Chinese PLA General Hospital China
Title: Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with sorafenib refractory hepatocellular carcinoma (HCC) and other solid tumors
Time : 11:50-12:50
Biography:
Weidong Han has obtained his PhD degree in Clinical Hematology from Chinese PLA Postgraduate Medical School in 2001 and worked in Department of Molecule & Immunology of Chinese PLA General Hospital. In 2003, he did Postdoctoral work at the University College London. In 2006, he was promoted to Professor of Molecular and Cellular Biology. Presently, he is the Director of Department of Molecular and Cellular Biology, Director of Clinical Translational Ward, the General Hospital of PLA. Since 2001, he focused on mechanism research involved in cancer treatment resistance and clinical translation of cell therapy. He has published over 80 articles.
Abstract:
CD133 is well documented to be expressed by tumor initiating cells and epithelial progenitor cells which were proposed to have predominant roles for tumor recurrence and pre-metastatic niche formation, respectively. Thus, targeting CD133 might help eradicate the primary tumors and even prevent tumor metastasis. Herein, CD133-directed chimeric antigen receptor modified T-cells (CART-133) were prepared and their specific targeting activity was verified. Results from hematopoietic colony forming assays suggested that CART-133 cells may pose no irreversible myelosuppression. Eight patients with advanced and sorafenib refractory HCC were enrolled on phase-I trial. They were assigned into 3 dose-escalated cohorts and were treated by repeated CART-133 monotherapy once 4-8 weeks. All patients had tolerable febrile syndromes during cell infusions. Rapid ascites growth occurred in 1 patient during infusion and was resolved by the use of diuretic. One patient developed transiently drastic decline of hemoglobin and platelets and Grade 3 direct hyperbilirubinemia within 2 weeks. Reverse correlation between CD133+ cells in PB and CAR copy number in cohort 2 and 3 revealed an effective biological activity of CART-133 and its rational expansion dose. 1 of 3 cases in cohort 1 aggressively progressed after cell therapy and became stable after transferred to cohort 2. Seven cases maintained stable disease so far, however, 2 patients died of upper gastrointestinal massive hemorrhage >9 weeks after infusion. Based on these, 7 additional patients with other metastatic solid tumors were enrolled into phase-II trial using the expansion dose, the response of which is under evaluation.
Hsu-Shan Huang
Taipei Medical University, Taiwan
Title: Drug development for EGFR-TKI resistance in non-small cell lung cancer cells: novel dual inhibitor of EGFR and cMET
Time : 13:50-14:50
Biography:
Hsu-Shan Huang has completed his Dr. rer. nat. at the age of 34 years from Regensburg University, Germany and pharmaceutical studies from NDMC School of Pharmacy. He was the dean of School of Pharmacy and director of R&D, NDMC. He has published more than 95 SCI papers and 30 patents in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide with a 5-year survival rate of less than 15% globally, accounting for more than 1.4 million deaths per year. Lung cancer is one of the most heavily mutated and genomically altered cancers. Despite the longer progression free survival of patients with TKI-treatment a high proportion eventually develop resistance. Resistance to targeted therapies is generally classified as either primary (i.e. intrinsic) or secondary (i.e. acquired). This approach has been variously termed “personalized cancer medicine”, “individualized cancer medicine” or “high precision cancer medicine”. Chemical synthesis led to further compound evaluations that revealed increased biochemical potency. The earliest efforts to utilize molecular profiling of tumors to guide more precise therapies for individual patients have met with remarkable success. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI-resistant tumors. We here provide evidence that NSC777201 (N19), a novel dual inhibitor of EGFR and cMET, efficiently overcomes the EGFR-TKI resistance in EGFR-mutated NSCLC cells via simultaneous degradation of both proteins by ubiquitin-proteasomes. In summary, N19 may act as a novel dual inhibitor of EGFR and cMET that induces apoptosis in TKI-resistant EGFR-mutated NSCLC cells and suppresses xenograft tumor formation. We suggest that N19 may be a potential new-generation TKI or HSP90 inhibitor used for treatment of NSCLC patients who show resistance to current TKItargeting therapies.
- 4 Immunotherapy-Tumors
9 Cancer Immunology & Immunotherapy
11 Cancer Research
13 Tumor immunotherapy research
14 Tumor markers and drug targetting
Location: Melbourne, Australia
Session Introduction
Maria Marcela Barrio
Centro de Investigaciones Oncológicas Fundación Cáncer, Argentina
Title: CSF-470 vaccine plus BCG plus rhGM-CSF show superiority vs. IFN-α2b in high risk cutaneous melanoma patients stages IIB, IIC and III: Interim results of the phase II part of phase II/III CASVAC0401 study
Time : 14:50-15:15
Biography:
Maria Marcela Barrio was graduated in 1991 as a Biologist at the University of Buenos Aires and obtained her PhD working on monoclonal antibodies at the Fundación Instituto Leloir. She became a Member of The National Scientific and Technical Research Council (CONICET) in 2007. She has been working in the cancer immunology as part of Dr. Mordoh´s team since 1984. Presently she is Sub-Director of the Centro de Investigaciones Oncológicas Fundación Cáncer. She has published more than 40 scientific papers about her specialty and she is working in translational research for the development of therapeutic vaccines for cutaneous melanoma.
Abstract:
Adjuvant treatment of high-risk cutaneous melanoma (CM) patients is still an unsolved issue. The CSF-470 therapeutic vaccine, a mixture of lethally irradiated allogeneic CM cell lines, combined with BCG and rhGM-CSF as adjuvants is currently tested in post-surgical adjuvancy against medium-dose IFN-α2b in stage IIB-III CM patients (CASVAC-0401 phase II-III study). Here we present the results of the phase II part of the study. Patients in the vaccine arm (n=20) received 1.6×107 CSF-470 melanoma irradiated cells i.d. plus 106 cfu BCG and 400 μg rhGM-CSF fractionated in 4 consecutive days were i.d. injected at the vaccination site, during 2 years (13 vaccinations in total). IFN-α2b patients (n=11) received 10 MU/day/5 days a week for 4 weeks; then 5 MU/day thrice weekly for 23 months (m). CSF-470 was well tolerated. The main toxicity was grade 2 reaction at the vaccination site (20/20); 3/20 patients presented grade 3 allergic reactions, easily handled with anti-histamines and corticosteroids; the rest of the AE were grade 1. IFN-α2b patients presented grade 2-3 hematologic (7/11), hepatic (2/11) and cardiac (1/11) toxicity, 9/11 patients developed AE that forced treatment discontinuation. QOL was significantly superior in CSF-470 arm vs. IFN-α2b arm. With a maximum follow-up of 72 m (Mean: 28 m) a significant benefit in the distant metastasis-free (DMF) survival for CSF-470 was observed (p=0.028). No significant differences in OS were yet observed. DTH reaction after the 7th vaccine was higher in distant metastasis-free patients than in progressing patients. Immune monitoring at 6 months showed an increase in NK cells (p=0.009) and a slight decrease in Tregs (p=0.021) in vaccinated patients; conversely IFN-α2b patients showed a significant decrease in total CD3+, CD4+ and CD8+T cells; serum Abs reactive with vaccine CM cells increased in all vaccinated patients (p<0.0001), but not in IFN-α2b patients. CSF-470 vaccine +BCG +GM-CSF superiority vs. IFN-α2b for adjuvant treatment of high-risk CM observed so far encourage continuation of the phase III part of CASVAC0401 study.
MarÃa del Rosario Dávalos Gamboa
University of San Simón, Bolivia
Title: Immune system, emotional problems and stress in kids and tenns with cancer of cochabamba, bolivia
Time : 15:15-15:40
Biography:
Maríadel Rosario Dávalos Gamboa has completed her PhD at the Universidad Mayor Real and Pontifical San Francisco Xavier de Chuquisaca, Bolivia and Specialty in Clinical Biochemistry and Immunology at University of San Simón in Cochabamba, Bolivia. She was the Director of the Research Institute of the Faculty of Dentistry at the University of San Simón in Cochabamba, Bolivia. She is currently a Professor of the subject of Biochemistry of Faculty of Dentistry UMSS and is also majority shareholder of the industrial unit" Asociada Internacional de aceites y carbones SRL ACECAB" of Bolivia. She has published more than 10 articles in leading journals.
Abstract:
Introduction: In the Plurinational State of Bolivia is little known as influenced, of the status immunological, emotional problems and stress in cancer of children and adolescents. Objectives: The objective of this study was to determine the influence they had, the immune system, emotional problems and stress for the development of different types of cancer in children and adolescents in the region of Cochabamba, Bolivia. Methods: Cross-sectional study realized in January and February 2016, in children and adolescents who regularly attend in Hospital Manuel Ascencio Villarroel, with aged 2 months to 16 years of age (n=45) in the region of Cochabamba (Bolivia). Parents and or guardians of participants were surveyed. A descriptive analysis was performed. Results: They had two or more signs and symptoms (low immunity) that the immune system was weakened 86.67%. They were usually affected by influenza and viruses 51.11% had muscle pain and joint constant 44.44%, had watery eyes and nose running 35.55%, had persistent headache 40%, much tired and fatigued despite the rest 35.56%, sick regularly 31.11%, was delayed recovery of disease 28.88%, exhibited a fixed pattern of disease 28.88% and quarreled endlessly with the disease 24.44%. They had two or more warning signs, symptoms and physical changes in stress 79.26%. Especially, headache and stomach 53.33%, disturbance in food 51.11%, they felt anxious 48.89%, were too sensitive 46.67%, were tired 44.44%, had nightmares 37.77 %, they were distracted or thoughtful 33.33%, were concerned 31.11%, her hands sweat 22.22%. They had one or more emotional problems mismanaged, for loss, failure or trauma 60.0%. Often they felt: Distressed 40%, depressed or anxious 37.78%, exhausted 33.33%, felt fear or loneliness 22.22%, angry 20%, extreme anxiety 15.56% and nervous anguish 15.56%. Conclusions: This study found that for the development of cancer suffered by children and adolescents, they influenced both mismanaged emotional problems, as stress and especially the immune system weakened in them, as a result of psychosomatic disorders that exposed them to the disease.
William Jia
University of British Columbia, ViroGin Biotech Ltd, Canada
Title: Oncolytic HSV-1 with enhancement of both oncolysis and safety
Time : 16:00-16:25
Biography:
William Jia has completed his PhD in 1991 at University of British Columbia (UBC) in Molecular Neurosciences. He has been an Associate Professor since 1999 at UBC and an Associate Scientist of BC Cancer Research Centre. He has been a Conjunct Professor of Fudan University, Shanghai Institute of Pharmaceutical Industry and the VP (research) for Shanghai Innovative Research Centre of Traditional Chinese Medicine (SIRC-TCM). He was the first in Canada and the first few scientists in the world using human Herpes simplex virus to treat cancer, which pioneered the field of oncolytic virotherapy for cancer treatment. He has developed one gene therapy drug for malignant gliomas has completed a phase I clinical trial in China. His most recent contribution is to raise the concept of transcription and translation dual regulated (TTDR) oncolytic viruses for cancer treatment. In the past years, he has received many awards and research funds. Since 1997, he has been a Scholar of Canadian Institute of Health Research. He has also received Petro Canada Young Inventors Award in 2007.
Abstract:
Oncolytic virotherapy has attracted increasing attention due to recent approval of T-VEC by FDA. Although anti-tumor immune response is a critical mechanism for oncolytic virotherapy, strong oncolytic viral activity for extensive cell lysis and virus dissemination inside of tumor also play a pivotal role for better therapeutic efficacy. However, it has always been a challenge to create an oncolytic virus that is highly oncolytic but also tumor specific for safety. In past years, we have been developing strategies that allow not only to enhance the safety but also to increase oncolytic activity at the same time. Those strategies include transcriptional and translational dual regulation on essential viral gene expression, overcoming macrophage/microglia barriers for better viral spreading in the tumor mass and enhancing virus oncolytic activity by inhibiting both anti-viral and oncogene cellular signals by a small molecule. We would present examples of those strategies and show their effects in animal tumor models.
Purwati
Universitas Airlangga, Indonesia
Title: The role of immunotherapy for stem cell cancer
Time : 16:00-16:25
Biography:
Purwati has finished in general practitioner from Airlangga University in 1997, has completed in internal med. Specialist in 2008 from Airlangga University also and taken Doctoral program in Airlangga University 2010-2012. Interest in stem cell field from 2008, be secretary of stem cell laboratory of Airlangga University and also secretary of Surabaya Regenerative Medicine Centre. 2015 be a chairman of stem cell research and development centre Universitas Airlangga Surabaya Indonesia. Have almost 50 publication in journals, papers, and seminar.
Abstract:
Aim: The role of immunotherapy for stem cell cancer. Method: Type of cancer are Carcinoma: Cancer of endo or ectoderm e.g., skin or epithelial lining of organs, Sarcomas: Cancer of mesoderm e.g., bone, Leukemias and Lymphomas: Cancers of hematopoietic cells. Molecular basis of cancer are dividing into three: The first is mutation was caused by radiation, chemicals and viruses; the second is up regulation of the proto oncogens and the third is down regulation of tumor suppressor genes. Cancer growth from cancer of stem cell with modality treatment of cancer was surgery, radiation, chemotherapy, Cryotherapy, radiofrequency, PBMCT, BMCT, until immunotherapy. Treatment modality was chosen depending on staging of cancer, but cancer of stem cell was known to resistance with conventional treatment, so for eliminated that the newest issue with immunotherapy. And also patients with metastasis staging of cancer usually also refracted with conventional treatment. So stem cell transplantation combination with immunotherapy will promise to give solution for that problem. Result: Haematopetic stem cell transplantation (HSCT) is a procedure to restoration bone marrow function as the result of giving cytotoxic drugs with or without whole body radiation. Source of stem cell from peripheral blood (PBMCs) or bone marrow or umbilical cord blood (UMCB) is autologus or allogenic. Conclusion: Stem cell combination with immunotherapy process was given separate or together, immunotherapy with NK cell or DCs autologous or allogenic. In vitro co culture between NK cell and leukemia cell, this cell could reduce the leukemia cell population, and also used in animal trial. Clinical trial on patient with solid tumor were treatment with immunotherapy with NK cell with the result of reducing of tumor size, with the reason because of NK cell have specific receptor as anti tumor, and also if given together with allogenic could prevent or decreasing rejection HSCT because of the unique properties of NK cell.
Qiaofei Liu
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, China
Title: Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection
Time : 16:25-16:50
Biography:
Qiaofei Liu has completed his MD at the age of 24 years from School of Medicine, Nankai University. He is now a attending surgeon of general surgery department in Peking Union Medical School College Hospital.His main interests are precise surgery and integrated treatments for pancreatic cancer. He has published more than 10 papers in reputed journals and has been serving as an editorial board member of 3 international journals.
Abstract:
Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86% of tumor tissue samples compared with 69% of peritumoral tissue samples (P = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade (P = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis (P = 0.01) in multivariate analysis. We further found that intratumoral M2 polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2 polarized TAMs probably induce IgG4-positive plasma cells.
George Kunudji
Asuboa traditional council hearth advocacy group, Ghana
Title: Cancer/testis antigens: an expanding family of targets for cancer immunotherapy
Time : 15:35-16:00
Biography:
george kunudji has completed his PhD at the age of 25 years from Andhra University and postdoctoral studies from Stanford University School of Medicine. He is the director of a premier Bio-Soft service organization. He has published more than 25 papers in reputed journals and has been serving as an editorial board member of repute
Abstract:
Cancer/testis (CT) antigens are a category of tumor antigens with normal expression restricted to male germ cells in the testis but not in adult somatic tissues. In some cases, CT antigens are also expressed in ovary and in trophoblast. In malignancy, this gene regulation is disrupted, resulting in CT antigen expression in a proportion of tumors of various types. Since their initial identification by T-cell epitope cloning, the list of CT antigens has been greatly expanded through serological expression cloning (SEREX) and differential mRNA expression analysis, and approximately 20 CT antigens or antigen families have been identified to date. Characteristics commonly shared by CT antigens, aside from the highly tissue-restricted expression profile, include existence as multigene families, frequent mapping to chromosome X, heterogeneous protein expression in cancer, likely correlation with tumor progression, induction of expression by hypomethylation and/or histone acetylation, and immunogenicity in cancer patients. Spontaneous humoral and cell-mediated immune responses have been demonstrated against several CT antigens, including NY-ESO-1, MAGE-A, and SSX antigens. Since CT antigens are immunogenic and highly restricted to tumors, their discovery has led directly to the development of antigen-specific cancer vaccines, and clinical trials with MAGE-A and NY-ESO-1 are in progress.