Search Our Scientific Publications & Authors

Immunity 2019 Feb 12;50(2):418-431.e6. Epub 2019 Feb 12.

Michael Smith Laboratories, University of British Columbia (UBC), 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada; The Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Department of Microbiology and Immunology, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Centre for Blood Research, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Department of Zoology, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Department of Medical Genetics, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. Electronic address:

Sepsis is a bi-phasic inflammatory disease that threatens approximately 30 million lives and claims over 14 million annually, yet little is known regarding the molecular switches and pathways that regulate this disease. Here, we have described ABCF1, an ATP-Binding Cassette (ABC) family member protein, which possesses an E2 ubiquitin enzyme activity, through which it controls the Lipopolysaccharide (LPS)- Toll-like Receptor-4 (TLR4) mediated gram-negative insult by targeting key proteins for K63-polyubiquitination. Ubiquitination by ABCF1 shifts the inflammatory profile from an early phase MyD88-dependent to a late phase TRIF-dependent signaling pathway, thereby regulating TLR4 endocytosis and modulating macrophage polarization from M1 to M2 phase. Read More

J Neurol Surg B Skull Base 2019 Feb 14;80(1):18-22. Epub 2018 Jun 14.

School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

 Perineural spread (PNS) is a marker of aggressiveness and has been shown to occur in cranial nerves due to advanced mucosal and cutaneous head and neck cancer. Receptors CXC chemokine receptor 4 (CXCR4) and programmed cell death-1 (PD-1) have been shown to be overexpressed in a variety of cancers with PNS, with the inhibition of these pathways offering a potential future treatment.  Retrospective immunohistochemical staining for the CXCR4 and PD-1 receptors was performed on 28 head and neck specimens that demonstrated PNS from January 2017 to August 2017, at Royal Brisbane and Women's Hospital, Brisbane, Australia. Read More

J Immunother Cancer 2019 Feb 6;7(1):33. Epub 2019 Feb 6.

NYU Langone Health, 522 First Avenue, 1306 Smilow Research Building, New York, NY, 10016, USA.

Background: Therapies targeting anti-tumor T-cell responses have proven successful in the treatment of a variety of malignancies. However, as most patients still fail to respond, approaches to augment immunotherapeutic efficacy are needed. Here, we investigated the ability of histone deacetylase 6 (HDAC6)-selective inhibitors to decrease immunosuppression and enhance immune function of melanoma patient T-cells in ex vivo cultures. Read More

Glycobiology 2019 Feb 6. Epub 2019 Feb 6.

Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen N, Denmark.

Successful application of potent antibody-based T-cell engaging immunotherapeutic strategies is currently limited mainly to hematological cancers. One major reason is the lack of well-characterized antigens on solid tumors with sufficient cancer specific expression. Aberrantly O-glycosylated proteins contain promising cancer-specific O-glycopeptide epitopes suitable for immunotherapeutic applications, but currently only few examples of such antibody epitopes have been identified. Read More

Curr Mol Med 2019 Feb 3. Epub 2019 Feb 3.

Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz. Iran.

Background: Cancer stem cells (CSCs) are a rare population of tumor cells, which play an important role in tumor initiation, progression, and maintenance. The concept that cancer cells arise from stem cells was presented about 150 years ago. Nowadays, because of the heterogeneity of tumor cells, this hypothesis has been renewed. Read More

Cancers (Basel) 2019 Jan 24;11(2). Epub 2019 Jan 24.

Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.

Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response. Read More

Ther Adv Urol 2019 Jan-Dec;11:1756287218815372. Epub 2019 Jan 8.

Section of Pathological Anatomy, Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, Ancona, Marche, I-60126, Italy.

Upper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1-2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Read More

Curr Hematol Malig Rep 2019 Jan 21. Epub 2019 Jan 21.

Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA.

Purpose Of Review: The treatment landscape for multiple myeloma has evolved rapidly with the availability of multiple new drugs; however, although patient survival has improved, the disease remains incurable. Multiple myeloma is characterized by the unregulated growth of malignant plasma cells accompanied by immune dysfunction as well as disrupted immune surveillance mechanisms. Here, we analyze clinical modalities, with a focus on monoclonal antibodies and adoptive cellular therapy that enhance patients' immune systems and overcome these defects. Read More

Am J Cancer Res 2018 1;8(12):2528-2537. Epub 2018 Dec 1.

Graduate Institute of Biomedical Sciences, China Medical University Taichung, Taiwan.

The E6 and E7 oncoproteins of human papillomavirus (HPV) are ideal targets for developing immunotherapeutic approaches to treat HPV-associated tumors. Our previous studies showed that a recombinant lipidated HPV16 E7 mutant (rlipo-E7m) with inactivation of the E7 oncogenic functions can activate antigen presenting cells through Toll-like receptor 2 (TLR2) and induce antitumor immunity. Given that some HPV-associated tumors overexpress E6 but not E7, it is necessary to include therapeutic agents containing HPV E6 in therapeutic vaccine development to broaden the utility of the vaccine. Read More

Vaccine 2019 Feb 17;37(7):926-936. Epub 2019 Jan 17.

School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China; Intenational Nanobody Research Center of Guangxi, Guangxi Medical University, Nanning, Guangxi 530021, China; National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address:

Tumor cells/dendritic cells (DCs) fusion cells (tumor/DC) represent a promising immunotherapeutic strategy but are still under performed in clinical trials for cancer treatment. To further boost their anticancer efficacy, here we developed a novel design for fusing dendritic cells with MDA-MB-231 cells expressing the heterologous α-galactose (α-gal) epitope and assessed its anticancer activities both in vitro and in vivo. The high expression of α-gal in MDA-MB-231 (Gal)/DC correlated with enhanced DC activation. Read More

Front Immunol 2018 21;9:3081. Epub 2018 Dec 21.

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.

Boosting natural immunity against malignant cells has had a major breakthrough in clinical cancer therapy. This is mainly due to the successful development of immune checkpoint blocking antibodies, which release a break on cytolytic anti-tumor-directed T-lymphocytes. However, immune checkpoint blockade is only effective for a proportion of cancer patients, and a major challenge in the field is to understand and overcome treatment resistance. Read More

J Gastrointest Surg 2019 Jan 8. Epub 2019 Jan 8.

Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the USA. Over 80% of CRC develop from adenomatous polyps. Hence, early treatment and prevention of adenomas would lead to a significant decrease of disease burden for CRC. Read More

Gut 2019 Jan 8. Epub 2019 Jan 8.

Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.

Objective: A hallmark of chronic HBV (cHBV) infection is the presence of impaired HBV-specific CD8+ T cell responses. Functional T cell exhaustion induced by persistent antigen stimulation is considered a major mechanism underlying this impairment. However, due to their low frequencies in chronic infection, it is currently unknown whether HBV-specific CD8+ T cells targeting different epitopes are similarly impaired and share molecular profiles indicative of T cell exhaustion. Read More

Open Forum Infect Dis 2018 Jul 26;5(7):ofy146. Epub 2018 Jun 26.

Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

e rarely causes pyogenic infections in the female genital tract, and even less commonly does this lead to systemic infections. Novel monoclonal antibody therapies targeting interleukin-17 may impair mucosal immunity, but increased risk for e infections has not been documented. Here, we describe a case of e bacteremia associated with pyosalpinx and hypothesize that immunomodulatory treatment for psoriasis predisposed our patient to this infection. Read More

Gut 2018 Dec 22. Epub 2018 Dec 22.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Objective: Chronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence indicates that functional cure of HBV infection by the host immune response is feasible. Read More

Blood Rev 2019 Mar 5;34:67-83. Epub 2018 Dec 5.

Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT, USA. Electronic address:

Immunotherapy has revolutionized therapy in both solid and liquid malignancies. The ability to cure acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an allogeneic hematopoietic stem cell transplant (HSCT) is proof of concept for the application of immunotherapy in AML and MDS. However, outside of HSCT, only the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin is currently approved as an antibody-targeted therapy for AML. Read More

Drug Discov Today Technol 2018 Dec 30;30:63-69. Epub 2018 Nov 30.

Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, United Kingdom. Electronic address:

Antibody conjugated nanoparticles (ACNPs) represent a novel strategy for the development of therapies exploiting antibodies to augment the delivery of chemotherapy payloads. Following in the footsteps of the success of antibody drug conjugates (ADCs), ACNPs are only now reaching clinical evaluation. In this review we discuss the success of ADCs and explore the opportunities ACNPs offer, such as broad chemotherapy payload selection, high drug to antibody ratios and the ability to finely tailor drug release in comparison to ADCs. Read More

Oncoimmunology 2019 16;8(1):e1514921. Epub 2018 Oct 16.

Lillian S. Wells Department of Neurosurgery, UF Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida, Gainesville, FL, USA.

Controversy surrounds the role of cytomegalovirus (CMV) in glioblastoma (GBM). However, several studies have shown that CMV nucleic acids and proteins are present within GBM tumor tissue. CMV has been implicated in GBM pathogenesis by affecting tumor stem cell factors, angiogenesis and immune pathways. Read More

J Virol 2019 Mar 19;93(5). Epub 2019 Feb 19.

Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA.

Eliciting highly functional CD8 cytotoxic T lymphocyte (CTL) responses against a broad range of epitopes will likely be required for immunotherapeutic control of HIV-1 infection. However, the combination of CTL exhaustion and the ability of HIV-1 to rapidly establish CTL escape variants presents major hurdles toward this goal. Our previous work highlighted the use of monocyte-derived, mature, high-interleukin-12 (IL-12)-producing type 1 polarized dendritic cells (MDC1) to selectively induce more potent effector CTLs derived from naive, rather than memory, CD8 T cell precursors isolated from HIV-1-positive participants in the Multicenter AIDS Cohort Study. Read More

Oncoimmunology 2018 21;7(12):e1500671. Epub 2018 Sep 21.

Department of Translational Immunology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Mutated proteins arising from somatic mutations in tumors are promising targets for cancer immunotherapy. They represent true tumor-specific antigens (TSAs) as they are exclusively expressed in tumors, reduce the risk of autoimmunity and are more likely to overcome tolerance compared to wild-type (wt) sequences. Hence, we designed a panel of long peptides (LPs, 28-35 aa) comprising driver gene mutations in and frequently found in gastrointestinal tumors to test their combined immunotherapeutic potential. Read More

Microb Pathog 2019 Feb 3;127:159-165. Epub 2018 Dec 3.

Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Staphylococcus aureus is a human commensal and pathogen, its clinical importance is exacerbated by the spread of multi-drug resistant strains. The potential future failure of antibiotic therapy necessitates the development of novel control regimes, including new immunotherapeutic approaches. S. Read More

Int J Mol Sci 2018 Dec 4;19(12). Epub 2018 Dec 4.

Department of Radiology, Biomolecular Theranostics (BiT) Lab, Chonnam National University Medical School, Hwasun 58128, South Korea.

Currently, immunotherapy is considered to be one of the effective treatment modalities for cancer. All the developments and discoveries in this field up to the recent Nobel Prize add to the interest for research into this vast area of study. Targeting tumor environment as well as the immune system is a suitable strategy to be applied for cancer treatment. Read More

Cancers (Basel) 2018 Nov 28;10(12). Epub 2018 Nov 28.

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Pancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis. Read More

Expert Opin Investig Drugs 2019 Jan 1;28(1):1-5. Epub 2018 Dec 1.

a Department of Obstetrics and Gynecology, Division of Molecular Oncology , University Medical Center , Mainz , Germany.

Introduction: Triple-negative breast cancer (TNBC) is associated with poor prognosis and limited treatment options. However, TNBC is known to be more immunogenic compared to other breast cancer subtypes, with tumor-infiltrating lymphocytes playing an important prognostic and predictive role. Furthermore, TNBC has a higher level of programmed cell death-ligand 1 (PD-L1) expression. Read More

Int J Biol Macromol 2019 Mar 22;124:17-24. Epub 2018 Nov 22.

Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India. Electronic address:

Epidermal growth factor receptor variant III (EGFRvIII) is known to be specifically expressed in cancer cells and associated with tumor virulence. The receptor provides an opportunity for both specifically targeting the tumor cells as well as for potentially controlling and inhibiting tumor progression. In this study, humanized anti-EGFRvIII single-chain fragment variable (hscFv) was expressed in insect cell culture system to accommodate post-translational glycosylations crucial for the fragment stability and efficacy. Read More

Best Pract Res Clin Haematol 2018 Dec 25;31(4):367-372. Epub 2018 Sep 25.

Pediatric Oncology Research Laboratory and Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, University of Chicago Medicine, Knapp Center for Biomedical Discovery, 900 E. 57th Street, 8th Floor Chicago, IL 60637, USA. Electronic address:

Survival rates in adult patients with acute lymphoblastic leukemia (ALL) have markedly improved during the past decade. The one-size-fits-all-ages approach has been replaced with adaptation of pediatric-inspired treatment protocols for younger adults. Yet different treatment strategies for older patients are needed due to chemotherapy-related toxicities. Read More

Int J Mol Sci 2018 Nov 15;19(11). Epub 2018 Nov 15.

Department of Dermatology, University Medical Center, 55131 Mainz, Germany.

Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses. Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies. This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far. Read More

J Crohns Colitis 2018 Nov 15. Epub 2018 Nov 15.

Department of Gastroenterology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.

Background And Aims: Macrophages are a promising therapeutic target for intestinal mucosal repair. MiR-146b appears to control macrophage activation and cell proliferation.

Methods: By loading miR-146b mimic on mannose-modified trimethyl chitosan (MTC)-conjugated nanoparticles (NPs) (MTC-miR146b), a molecular targeted immunotherapeutic approach was developed to selectively target intestinal macrophages for mucosal regeneration and tumourigenesis in mouse models. Read More

Cancer Cell 2018 Nov;34(5):757-774.e7

S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 435 East 30th Street, 4th Floor, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. Electronic address:

Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 (RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Read More

Biosens Bioelectron 2019 Feb 25;126:178-186. Epub 2018 Oct 25.

Centre for Personalised Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD 4072, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

Immune checkpoint blockade therapies are promising next generation immunotherapeutic treatments for cancer. Whilst sequential solid biopsies are an invaluable source of prognostic information, they are not feasible for monitoring therapeutic outcomes over time. Monitoring soluble immune checkpoint markers expression in body fluids could potentially be a better alternative. Read More

Pharm Res 2018 Nov 8;36(1). Epub 2018 Nov 8.

Discipline of Pharmaceutics, School of Pharmacy, University of the Western Cape, Cape Town, South Africa.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a deadly infectious disease. The thin pipeline of new drugs for TB, the ineffectiveness in adults of the only vaccine available, i.e. Read More

Expert Rev Proteomics 2018 Dec 14;15(12):1065-1077. Epub 2018 Nov 14.

a Center for Personalized Diagnostics, Biodesign Institute , Arizona State University , Tempe , AZ , USA.

Introduction: The recent development of checkpoint blockade immunotherapy for cancer has led to impressive clinical results across multiple tumor types. There is mounting evidence that immune recognition of tumor derived MHC class I (MHC-I) restricted epitopes bearing cancer specific mutations and alterations is a crucial mechanism in successfully triggering immune-mediated tumor rejection. Therapeutic targeting of these cancer specific epitopes (neoepitopes) is emerging as a promising opportunity for the generation of personalized cancer vaccines and adoptive T cell therapies. Read More

Ann Oncol 2019 Jan;30(1):68-75

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou.

Background: Targeting the immune checkpoint pathway has demonstrated antitumor cytotoxicity in treatment-refractory head and neck squamous cell carcinoma (HNSC). To understand the molecular mechanisms underpinning its antitumor response, we characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups.

Patients And Methods: A training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. Read More

J Immunol 2018 Dec 5;201(12):3731-3740. Epub 2018 Nov 5.

Department of Surgery, Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210; and

Humoral alloimmunity negatively impacts both short- and long-term cell and solid organ transplant survival. We previously reported that alloantibody-mediated rejection of transplanted hepatocytes is critically dependent on host macrophages. However, the effector mechanism(s) of macrophage-mediated injury to allogeneic liver parenchymal cells is not known. Read More

Expert Opin Biol Ther 2018 Dec 13;18(12):1209-1221. Epub 2018 Nov 13.

a Myeloma Unit, Division of Hematology , University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino , Torino , Italy.

Introduction: Multiple myeloma (MM) is a currently incurable hematologic tumor with heterogeneous clinical behavior and prognosis. During the last years, survival improved due to a better understanding of MM biology and the development of novel drugs, although it still remains unsatisfactory in many cases: new drugs and treatment strategies are needed. CD38 is uniformly expressed at high levels on MM cells and, to a lesser extent, on the surface of normal hematopoietic and non-hematopoietic cells, making this molecule an interesting target for immunotherapeutic approaches. Read More

Biomaterials 2019 Jan 29;190-191:38-50. Epub 2018 Oct 29.

Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, South Korea. Electronic address:

Purpose: Natural killer (NK) cells are the key subset of innate-immunity lymphocytes; they possess antitumor activities and are used for cancer immunotherapy. In a previous study, extracellular vehicles (EVs) from NK-92MI cells were isolated and exploited for their ability to kill human cancer cells in vitro and in vivo (multiple injection methods). Here, the potential of NK-cell-derived EVs (NK-EVs) for immunotherapy was improved by priming with interleukin (IL)-15. Read More

Cancer Immunol Immunother 2018 Dec 2;67(12):1955-1965. Epub 2018 Nov 2.

Molecular Pathology Section, Laboratory of Immunogenetics, NIAID/NIH, Twinbrook 1, Room 1329, 5640 Fishers Lane, Rockville, MD, 20852, USA.

Cancer vaccines have great potential in the fight against metastatic malignancies. Current anti-tumor immunotherapy is hindered by existing tolerance to tumor-associated antigens (TAA) and tumor escape using various mechanisms, highlighting the need for improved targets for immunotherapy. The cancer-testis antigen CTCFL/BORIS was discovered 16 years ago and possesses all features necessary for an ideal TAA. Read More

Front Oncol 2018 17;8:453. Epub 2018 Oct 17.

Department of Neurosurgery, IU Simon Cancer Center, IU School of Medicine, Indiana University Purdue University Indianapolis, Indianapolis, IN, United States.

T cell chimeric antigen receptor (CAR) technology has allowed for the introduction of a high degree of tumor selectivity into adoptive cell transfer therapies. Evolution of this technology has produced a robust antitumor immunotherapeutic strategy that has resulted in dramatic outcomes in liquid cancers. CAR-expressing T-cells (CARTs) targeting CD19 and CD20 have been successfully used in the treatment of hematologic malignancies, producing sustained tumor regressions in a majority of treated patients. Read More

Biomater Sci 2019 Jan;7(2):547-559

Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA.

RNA agonists of the retinoic acid gene I (RIG-I) pathway have recently emerged as a promising class of cancer immunotherapeutics, but their efficacy is hindered by drug delivery barriers, including nuclease degradation, poor intracellular uptake, and minimal access to the cytosol where RIG-I is localized. Here, we explore the application of pH-responsive, endosomolytic polymer nanoparticles (NPs) to enhance the cytosolic delivery and immunostimulatory activity of synthetic 5' triphosphate, short, double-stranded RNA (3pRNA), a ligand for RIG-I. Delivery of 3pRNA with pH-responsive NPs with an active endosomal escape mechanism, but not control carriers lacking endosomolytic activity, significantly increased the activity of 3pRNA in dendritic cells, macrophages, and cancer cell lines. Read More

Br J Cancer 2019 Jan 31;120(1):97-108. Epub 2018 Oct 31.

Department of Laboratory Medicine (LABMED), Division of Therapeutic Immunology (TIM), Karolinska Institutet, Stockholm, Sweden.

Background: Pancreatic cancer exhibits a poor prognosis and often presents with metastasis at diagnosis. Immunotherapeutic approaches targeting private cancer mutations (neoantigens) are a clinically viable option to improve clinical outcomes.

Methods: 3/40 TIL lines (PanTT26, PanTT39, PanTT77) were more closely examined for neoantigen recognition. Read More

Int J Mol Sci 2018 Oct 26;19(11). Epub 2018 Oct 26.

Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA.

Within the subtypes of breast cancer, those identified as triple negative for expression of estrogen receptor α (ESR1), progesterone receptor (PR) and human epidermal growth factor 2 (HER2), account for 10⁻20% of breast cancers, yet result in 30% of global breast cancer-associated deaths. Thus, it is critical to develop more targeted and efficacious therapies that also demonstrate less side effects. Selenium, an essential dietary supplement, is incorporated as selenocysteine (Sec) in vivo into human selenoproteins, some of which exist as anti-oxidant enzymes and are of importance to human health. Read More

Recent Pat Anticancer Drug Discov 2018 Oct 29. Epub 2018 Oct 29.

College of Biomedical and Health Sciences, Konkuk University, Chungju 27478. Korea.

Background: In the last few decades, cancer immunotherapy has been extensively researched, and novel checkpoint signaling mechanisms involving programmed death (PD)-1 and PD-ligand 1 (PD-L1) receptors have been targeted. The PD-1/PD-L1 binding and interaction play a critical role in the development of malignancies.

Objective: The present review focuses on recent patents on the pharmacological and biological cancer-regulating properties of PD-1/PD-L1 inhibitors involved in immunotherapeutic cancer drug development. Read More

J Pharmacol Exp Ther 2019 Jan 25;368(1):106-115. Epub 2018 Oct 25.

Section for Drug Abuse Research, Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway (A.M.S.K., J.M.A., E.L.Ø., S.S., I.L.B.); School of Pharmacy, Faculty of Mathematics and Natural Sciences (A.M.S.K., J.M.A., E.L.Ø.), Institute of Basic Medical Sciences (I.L.B.) and Institute of Clinical Medicine (J.M.), Faculty of Medicine, University of Oslo, Oslo, Norway; and Department of Infectious Disease Immunology (A.A.) and Department of Health Data and Digitalization (J.M.), Norwegian Institute of Public Health, Oslo, Norway

Escalating opioid use among fertile women has increased the number of children being exposed to opioids during fetal life. Furthermore, accumulating evidence links prenatal opioid exposure, including opioid maintenance treatment, to long-term negative effects on cognition and behavior, and presses the need to explore novel treatment strategies for pregnant opioid users. The present study examined the potential of a monoclonal antibody (mAb) targeting heroin's first metabolite, 6-acetylmorphine (6-AM), in providing fetal protection against harmful effects of prenatal heroin exposure in mice. Read More

Urol Oncol 2018 Oct 17. Epub 2018 Oct 17.

Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada; Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada. Electronic address:

Over the past decade, genomic and transcriptomic analyses have uncovered promising tumor antigens including immunotherapeutic targets in bladder cancer (BCa). Conventional tumor antigens are proteins expressed on the plasma membrane of tumor cells such as EGFR, FGFR3, and ERBB2 in BCa, which can be targeted by antibodies or similar epitope-specific binding reagents. The cellular proteome consists of ∼100,000 proteins but the expression of these proteins is rarely unique to tumor cells. Read More

Front Oncol 2018 4;8:423. Epub 2018 Oct 4.

Division of Medical Oncology, University of Kansas Medical Center, Fairway, KS, United States.

Recent application of immunotherapy in clinical oncology revolutionized our management of advanced human cancers. Check point inhibitors targeting CTLA4 and PD-1/PD-L1 axis are immunotherapeutic agents currently available to treat a variety of cancers. However, a novel therapeutic approach is needed to further improve patient outcome with these agents. Read More

Clin Cancer Res 2019 Feb 16;25(3):1036-1049. Epub 2018 Oct 16.

Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.

Purpose: Adoptive T-cell therapy (ACT) of cancer, which involves the infusion of -engineered tumor epitope reactive autologous T cells into the tumor-bearing host, is a potential treatment modality for cancer. However, the durable antitumor response following ACT is hampered either by loss of effector function or survival of the antitumor T cells. Therefore, strategies to improve the persistence and sustain the effector function of the antitumor T cells are of immense importance. Read More

Immunity 2018 Oct 9;49(4):678-694.e5. Epub 2018 Oct 9.

Princess Margaret Cancer Center, University Health Network, Toronto, ON, M5G 2M9 Canada; Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8 Canada. Electronic address:

CD8 T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8 T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1 cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy. Mechanistically, adaptations of antigen-presenting cells and diminished T cell signaling intensity promoted differentiation of the memory-like subset at the expense of rapid effector cell differentiation, which was now highly dependent on IL-21-mediated CD4 T cell help for its functional generation. Read More

Crit Rev Oncol Hematol 2018 Nov 1;131:1-6. Epub 2018 Aug 1.

Oncology Unit, City Hospital, Faenza, Italy.

Telomerase activity and telomere length are essential for the pathogenesis of several human diseases, including genitourinary tumors. Telomerase constitutes a complex system that includes human telomerase reverse transcriptase (hTERT), human telomerase RNA component (hTR) and telomerase associated protein 1 (TEP1), which are overexpressed in tumor cells compared to normal cells and are involved in the carcinogenesis and progression of renal cell carcinoma (RCC), bladder (BC) and prostate cancer (PCa). In addition, telomerase degraded peptide fragments expressed on the surface of tumor cells lead to their recognition by immune cells. Read More

Oncoimmunology 2018 26;7(10):e1486952. Epub 2018 Jul 26.

The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia.

Immunomodulatory therapies can effectively control haematological malignancies. Previously we reported the effectiveness of combination immunotherapies that centre on 4-1BB-targeted co-stimulation of CD8 + T cells, particularly when simultaneously harnessing the immune adjuvant properties of Natural Killer T (NKT) cells. The objective of this study was to assess the effectiveness of agonistic anti-4-1BB antibody-based combination therapy against two aggressive forms of acute myeloid leukemia (AML). Read More

MBio 2018 10 2;9(5). Epub 2018 Oct 2.

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany

is a common airborne fungal pathogen of humans and a significant source of mortality in immunocompromised individuals. Here, we provide the most extensive cell wall proteome profiling to date of resting conidia, the fungal morphotype pertinent to first contact with the host. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified proteins within the conidial cell wall by hydrogen-fluoride (HF)-pyridine extraction and proteins exposed on the surface using a trypsin-shaving approach. Read More