Breaking News
July 21, 2018 - ADHD medications may fail to improve cognition in healthy college students, study shows
July 21, 2018 - Intervention program that includes a personalized app could benefit teens with suicidal thoughts
July 21, 2018 - Researchers identify new compound that protects against neurodegeneration
July 21, 2018 - Gene therapy may hold potential to treat people with spinal cord injuries
July 21, 2018 - FDA Approves Nivestym (filgrastim-aafi), a Biosimilar to Neupogen
July 21, 2018 - Surgeons have substantial impact on genetic testing in breast cancer patients who need it
July 21, 2018 - Species diversity can have positive and negative impacts on disease transmission
July 21, 2018 - Genome research suggests presence of enteric fever in medieval Europe
July 21, 2018 - Risk of Sensory Deficits Drops With Rising Gestational Age
July 21, 2018 - Mum’s sleep matters—the effect of sleep on an unborn baby
July 21, 2018 - UC San Diego researchers awarded two grants for investigating stem cell-based therapies
July 21, 2018 - Cellular ‘garbage disposal’ may actually work on some of the proteins to neuronal development
July 21, 2018 - More Pregnant Women Having Heart Attacks
July 21, 2018 - Acne Breakouts | NIH News in Health
July 21, 2018 - Change health messaging to focus on potential impact to help stop the next pandemic
July 21, 2018 - Frailty associated with poor survival rates in young heart patients
July 21, 2018 - New discovery could save millions of lives from fatal fungal infections
July 21, 2018 - OBD presents latest data on the use of EpiSwitch™ in predicting patient response to immunotherapy and identifying lymphoma subtypes
July 21, 2018 - Childhood adversity increases susceptibility to addiction via immune response
July 21, 2018 - Scientists identify potential target for the treatment of binge eating
July 21, 2018 - Whole-brain LIPUS therapy improves cognitive dysfunction in mice simulating dementia, Alzheimer’s
July 21, 2018 - Digital media use raising risk of ADHD symptoms among the young
July 21, 2018 - Phase 3 study of tanezumab in patients with osteoarthritis pain meets all three co-primary endpoints
July 21, 2018 - Restoring mitochondrial function to reverse aging-related skin wrinkles, hair loss in mice
July 21, 2018 - SP PennTech introduces RW-500 rotary vial washer for biotech, pharmaceutical applications
July 21, 2018 - Researchers to study molecular mechanisms behind susceptibility of males to autism
July 21, 2018 - Researchers study efficacy and safety of new treatment for OUD
July 21, 2018 - Fourth Published Clinical Trial Confirms Long-Term Safety of Niagen Supplementation at High Doses and Shows Potential for Improvement in Liver Health
July 21, 2018 - Study examines effects of a two-day intermittent calorie restriction diet for patients with type 2 diabetes
July 21, 2018 - Greening vacant urban land reduces feelings of depression for surrounding residents
July 21, 2018 - Parents say intense gun violence in PG-13 movies appropriate for teens 15 and older
July 21, 2018 - Collaborative study to assess effects of exercise training for cognitive deficits in MS
July 21, 2018 - FAU researchers find possible cause of Parkinson’s disease in the patients’ immune system
July 21, 2018 - Protective qualities of ‘good cholesterol’ reduce after menopause
July 21, 2018 - Researchers develop new way to uncover hidden breast cancer tumors
July 21, 2018 - FDA approves first drug for treatment of adult AML patients with specific genetic mutation
July 21, 2018 - Top AI companies join hands to discover novel drugs for DMD
July 21, 2018 - Ferring announces FDA approval of ZOMACTON for injection in four new pediatric indications
July 20, 2018 - Researchers design proteins that can self-assemble into complex structures
July 20, 2018 - AVITA Medical expands management team to support launch of RECELL device to treat burns
July 20, 2018 - FDA Approves Tibsovo (ivosidenib) for Relapsed or Refractory Acute Myeloid Leukemia with an IDH1 Mutation
July 20, 2018 - Developmental screening and surveillance rates remain low, new study suggests
July 20, 2018 - TGen opens tissue donation portal to advance DIPG research
July 20, 2018 - Health impact of highly processed summertime staples
July 20, 2018 - Exergaming can improve health in overweight and obese children, study shows
July 20, 2018 - Postmenopausal factors may impact heart-protective qualities of ‘good cholesterol’
July 20, 2018 - MRI and blood test combination results in improved prostate cancer diagnosis
July 20, 2018 - Update Health Professional and Consumer on Recent Recalled Products
July 20, 2018 - Researchers trace Parkinson’s damage in the heart
July 20, 2018 - Wearable device designed to measure cortisol in sweat
July 20, 2018 - Scientists demonstrate a new regulation mechanism for skeletal muscles
July 20, 2018 - Exposure to mobile phone radiation may negatively impact memory performance in adolescents
July 20, 2018 - SUSU scientists find alternative method to treat post-traumatic stress disorder syndrome
July 20, 2018 - Gestational diabetes may increase offspring’s heart disease risk
July 20, 2018 - New vaccine could protect unborn babies from Zika virus
July 20, 2018 - Researchers find high mercury and methylmercury concentrations in traditional Tibetan medicine
July 20, 2018 - Brief Safety Plan Intervention in ER Can Cut Suicidal Behavior
July 20, 2018 - The Mount Sinai Hospital receives accreditation as geriatric emergency department
July 20, 2018 - Toward a better understanding of Parkinson’s disease
July 20, 2018 - Med school communications office wins four national awards | News Center
July 20, 2018 - Professional baseball players with faster hand-eye coordination may have better batting performance
July 20, 2018 - Study looks into mechanisms that control sleep and wakefulness
July 20, 2018 - Scientists identify melanoma biomarkers that could help tailor immunotherapy treatments
July 20, 2018 - Research reveals long-term efficacy of drug used to treat common cause of kidney failure
July 20, 2018 - Timing of dinner associated with breast and prostate cancer risks
July 20, 2018 - Health Tip: Performing the Heimlich Maneuver
July 20, 2018 - Nearly all adolescents have eating, activity or weight-related issues
July 20, 2018 - Sage launches new web-based tool that helps explore curated genomic analyses of Alzheimer’s
July 20, 2018 - High-performance porous polymeric material for chromatography applications
July 20, 2018 - New molecule shows great promise for future treatment of many cancers
July 20, 2018 - New research project investigates alternative treatments for eye infections
July 20, 2018 - Immune T cells are built to react as fast as possible, shows study
July 20, 2018 - ZHX2 protein could offer a new treatment strategy for kidney cancer
July 20, 2018 - EKF’s Quo-Lab POC HbA1c analyzer meets international quality targets for diabetes testing
July 20, 2018 - Health burdens of very high risk drinking are potentially large, study reveals
July 20, 2018 - Using miniature drug-filled nanocarriers to target headaches and tumors
July 20, 2018 - Researchers uncover cause for progression of prostate cancer to incurable stage
July 20, 2018 - Studies highlight issues regarding black lung, opioid overdose, police violence and more
July 20, 2018 - AbbVie submits supplemental NDA to FDA for venetoclax to treat acute myeloid leukemia
July 20, 2018 - Researchers are one step closer to developing eye drops to treat age-related macular degeneration (AMD)
Personalized T cell therapy shows signs of clinical effectiveness against HBV-related HCC

Personalized T cell therapy shows signs of clinical effectiveness against HBV-related HCC

image_pdfDownload PDFimage_print

Multiple adoptive transfers of T cells engineered to carry hepatitis B virus (HBV)-specific T cell receptors (TCRs) has resulted in an objective positive response in a patient with hepatitis B surface antigen (HBsAg)-negative HCC metastases in the lungs following liver transplant. The patient, described today in a presentation at The International Liver Congress 2018 in Paris, France, had a volumetric reduction of almost all lung lesions and no new lesions detected in the lung or liver.

HCC is the most common primary liver cancer and more than 50% of cases around the world are thought to be associated with chronic HBV., With a poor prognosis and limited therapeutic options, HCC is the second most common cause of cancer mortality worldwide. Liver transplantation is an option for some patients but HCC recurs in up to 20% of cases, with the lungs the most common site of metastases. Cytotoxic T cells play a key role in killing cancerous and infected cells when TCRs on their surface recognize short epitopes presented on the affected cell’s surface and initiate a series of cytotoxic mechanisms. In HBV-related HCC tumours, integrated HBV DNA can result in both oncogenic transformation and expression of HBV epitopes on the cell surface.

“We hypothesized that HBV transcriptomic profiles of HCC cells could guide the selection of HBV-specific TCRs to be used in engineering T cells for HCC-targeted immunotherapy.” explained Dr. Anthony Tan from the Emerging Infectious Diseases Programme at Duke-NUS Medical School in Singapore, the lead author of the study. “We first had to test if short, integrated HBV DNA fragments in tumour cells can produce HBV epitopes recognized by cytotoxic T cells.”

Characterization of the expression of short, specific regions of integrated HBV DNA in natural HBV-related HCC lines negative for serological markers of HBV infection identified HBV epitopes that were functionally presented on the cell surface. These HCC cells could be lysed in vitro by T cells engineered to express TCRs specific for the epitopes that had been identified. A similar analysis was able to identify a region of HBV envelope encoded by integrated HBV DNA fragments derived from the primary HCC of a liver transplant patient with HBsAg-negative HCC metastases in the lungs. The TCR specific for this HBV envelope region was introduced into T cells using mRNA electroporation. Multiple adoptive transfers of the resulting HBV-specific TCR T cells into the patient were performed over a period of 6 months.

No therapy-related adverse events were observed, and computed tomography imaging performed before and during therapy showed an objective positive response with a volumetric reduction of nearly all lung lesions detected, with no new lesions detected in the lung or liver to date. As of January 2018, the tumour lesions in the lung remain stable.

“The use of mRNA electroporation for exogenous TCR expression reduces the potential toxicity of this approach compared with previous techniques using viral vectors,” said Dr. Tan. “Further development of this new immunotherapeutic strategy may offer new hope of a cure for HCC.”

“This study further explores the potentially beneficial role of immunotherapy in the management of advanced HCC,” said Prof. Alejandro Forner from the Hospital Clinic Barcelona, Spain, and EASL Governing Board Member. “With this interesting approach, the authors have been able to develop a personalized T cell adoptive immunotherapy for patients with HBV-related HCC with promising signs of clinical effectiveness. Further studies will be needed to confirm that this strategy is a viable option for patients.”


Explore further:
Immunotherapy could help tackle tough liver cancer

Provided by:
European Association for the Study of the Liver

Tagged with:

About author

Related Articles