A5079086232- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Research and Treatments
- CAR-T cell therapy research
- Spine and Intervertebral Disc Pathology
- Spinal Fractures and Fixation Techniques
- Cervical and Thoracic Myelopathy
- Attention Deficit Hyperactivity Disorder
- Functional Brain Connectivity Studies
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Musculoskeletal pain and rehabilitation
- Anesthesia and Pain Management
- Advanced Neuroimaging Techniques and Applications
- Viral gastroenteritis research and epidemiology
- Biomedical and Engineering Education
- Cerebrospinal fluid and hydrocephalus
- Neural and Behavioral Psychology Studies
- Cancer, Hypoxia, and Metabolism
- Vascular Malformations Diagnosis and Treatment
- Health Systems, Economic Evaluations, Quality of Life
- Alcohol Consumption and Health Effects
- Bacterial Identification and Susceptibility Testing
- Cognitive Abilities and Testing
- Neuroblastoma Research and Treatments
University of Helsinki
2012-2024
Helsinki University Hospital
2010-2024
Hospital District of Helsinki and Uusimaa
2024
Data Harbor (United States)
2015
Oncos Therapeutics (Finland)
2013
Institute for Molecular Medicine Finland
2010-2011
Augmenting antitumor immunity is a promising way to enhance the potency of oncolytic adenoviral therapy. Granulocyte–macrophage colony–stimulating factor (GMCSF) can mediate effects by recruiting natural killer cells and induction tumor-specific CD8+ cytotoxic T-lymphocytes. Serotype 5 adenoviruses (Ad5) are commonly used in cancer gene However, expression coxsackie-adenovirus receptor variable many advanced tumors preclinical data have demonstrated an advantage for replacing Ad5 knob with...
Abstract Purpose: Multiple injections of oncolytic adenovirus could enhance immunologic response. In the first part this article, focus was on aspects. Sixty patients previously naïve to virus and who had white blood cells available were treated. Thirty-nine 60 assessed after a single administration, whereas 21 received “serial treatment” consisting three within 10 weeks. second part, we focused 115 treated with granulocyte macrophage colony-stimulating factor (GM–CSF)–coding capsid chimeric...
Oncolytic adenoviruses and certain chemotherapeutics can induce autophagy immunogenic cancer cell death. We hypothesized that the combination of oncolytic adenovirus with low-dose temozolomide (TMZ) is safe, effective, capable inducing antitumor immune responses. Metronomic cyclophosphamide (CP) was added to selectively reduce regulatory T-cells. Preclinically, therapy inhibited tumor growth, increased autophagy, triggered death as indicated by elevated calreticulin, adenosine triphosphate...
Patients with advanced solid tumors refractory to and progressing after conventional therapies were treated three different regimens of low-dose cyclophosphamide (CP) in combination oncolytic adenovirus. CP was given oral metronomic dosing (50 mg/day, N = 21), intravenously (single 1,000 mg dose, 7) or both (N 7). Virus injected intratumorally. Controls 8) received virus without CP. Treatments well tolerated safe regardless schedule. Antibody formation replication not affected by Metronomic...
// Otto Hemminki 1 , Suvi Parviainen Juuso Juhila Riku Turkki 2 Nina Linder Johan Lundin 2, 3 Matti Kankainen 4 Ari Ristimäki 5 Anniina Koski Ilkka Liikanen Minna Oksanen Dirk M. Nettelbeck 6 Kalevi Kairemo 7 Kaarina Partanen Timo Joensuu Anna Kanerva 1, 8 Akseli 7, 9 Cancer Gene Therapy Group, Transplantation Laboratory & Haartman Institute, University of Helsinki, Finland Institute for Molecular Medicine (FIMM), Division Global Health/IHCAR, Karolinska Institutet, Stockholm,...
With the emergence of effective immunotherapeutics, which nevertheless harbor potential for toxicity and are expensive to use, biomarkers urgently needed identification cancer patients who respond treatment. In this clinical-epidemiological study 202 treated with oncolytic adenoviruses, we address biomarker value serum high-mobility group box 1 (HMGB1) protein. Overall survival imaging responses were studied as primary endpoints adjusted confounding factors in two multivariate analyses (Cox...
Individuals with attention-deficit/hyperactivity disorder (ADHD) have difficulties navigating dynamic everyday situations that contain multiple sensory inputs need to either be attended or ignored. As conventional experimental tasks lack this type of complexity, we administered a film-based multi-talker condition auditory distractors in the background. ADHD-related aberrant brain responses naturalistic stimulus were identified using intersubject correlations (ISCs) functional magnetic...
Metastatic melanoma is refractory to irradiation and chemotherapy, but amenable immunological approaches such as immune‐checkpoint‐inhibiting antibodies or adoptive cell therapies. Oncolytic virus replication an immunogenic phenomenon, viruses can be armed with immunostimulatory molecules. Therefore, oncolytic immuno‐virotherapy of malignant appealing approach, which was recently validated by a positive phase 3 trial. We investigated the potency adenovirus Ad5/3‐D24‐GMCSF on panel lines...
Sarcomas are a relatively rare cancer, but often incurable at the late metastatic stage. Oncolytic immunotherapy has gained attention over past years, and wide range of oncolytic viruses have been delivered via intratumoral injection with positive safety promising efficacy data. Here, we report preclinical clinical results from treatment sarcoma adenovirus Ad5/3-D24-GMCSF (CGTG-102). is serotype chimeric coding for human granulocyte-macrophage colony-stimulating factor (GM-CSF). The was...
Breast cancer is a heterogeneous disease, characterized by several distinct biological subtypes, among which triple-negative breast (TNBC) one associated with poor prognosis. Oncolytic virus replication an immunogenic phenomenon, and viruses can be armed immunostimulatory molecules to boost triggered antitumoral immune responses. Cyclophosphamide (CP) chemotherapy drug that cytotoxicity immunosuppression at higher doses, whereas anti-angiogenic properties are observed low continuous dosage....
The development of oncolytic viruses has recently made great progress towards being available to cancer patients. With the breakthrough into clinics, it is crucial analyze existing clinical experience and use as a basis for treatment improvements. Here, we report data from 290 patients treated with adenovirus. Using variables characteristics, constructed statistical models regard response overall survival (OS). Additionally, investigated effects neutralizing antibodies, tumor burden,...
Abstract Background Lumbar disc herniation is often managed conservatively; nevertheless, surgical intervention can be required. Majority of patients experience a drastic relief symptoms after surgery, but previous studies have reported that their health-related quality life remains inferior compared to the general population for several years. There may major cumulative loss young as they long expected ahead them. Methods A total 526 eligible adult under age 40 underwent surgery lumbar from...
Calcium channel blockers including verapamil have been proposed to enhance release and antitumor efficacy of oncolytic adenoviruses in preclinical studies but this has not studied humans before. Here, we if leads increased replication adenovirus cancer patients, as measured by virions from tumor cells into the systemic circulation. The study was conducted a matched case-control advanced patients treated with or without verapamil. We observed that mean virus titers present blood after...
In clinical trials with oncolytic adenoviruses, there has been no mortality associated treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated 10 different viruses, vector-related was observed. However, as patient population who received adenovirus treatments ATAP represented heavily pretreated patients, often very advanced disease, some died relatively soon after receiving their virus mandating autopsy to investigate cause of death. Eleven...
Rapid clearance of adenoviruses from blood by macrophage lineage cells the liver and spleen, binding to platelets, hinder their successful systemic use for cancer gene therapy. Vitamin K dependent coagulation factors are important mediators adenovirus tropism. Here we aim determine effects factor, thrombocyte (Kupffer cell) ablation on biodistribution serotype 5 in mice with orthotopic breast tumors.Prior intravenous injection adenoviruses, bearing tumors were pretreated warfarin inhibit...
Computed tomography (CT) is the most commonly used radiological response evaluation method in contemporary oncology. However, it may not be optimally suitable for assessment of oncolytic virus treatments because paradoxical inflammatory tumor swellings, which result from treatments, particularly when viruses are armed with immunostimulatory molecules. Here we investigated prognostic utility CT and [18F]-fluorodeoxyglucose (FDG) positron emission (PET) treatments. We also possible appearance...
Despite many clinical trials conducted with oncolytic viruses, the exact tumor-level mechanisms affecting therapeutic efficacy have not been established. Currently there are no biomarkers available that would predict outcome to any virus. To assess baseline immunological phenotype and find potential prognostic biomarkers, we monitored mRNA expression levels in 31 tumor biopsy or fluid samples from 27 patients treated adenovirus. Additionally, protein was studied 19 biopsies using...
Drugs and alcohol often occur together in fatal poisonings, complicating the process of determining cause death. Especially when found concentrations generally regarded as toxic but not lethal, question arises whether combination sublethal amounts was likely In this study, we examined poisoning deaths involving amitriptyline, propoxyphene promazine, which are, after benzodiazepines, most frequently occurring drugs Finnish alcohol-related poisonings. From forensic toxicology database,...
At present, it is not possible to reliably identify patients who will benefit from oncolytic virus treatments. Conventional modalities such as computed tomography (CT), which measure tumor size, are unreliable owing inflammation‐induced swelling. We hypothesized that magnetic resonance imaging (MRI) and spectroscopy (MRS) might be useful in this regard. However, little previous data exist neither adenovirus nor immunocompetent models have been assessed by MRS. Here, we provide evidence...
Abstract The development of treatments for attention impairments is hampered by limited knowledge about the malleability underlying neural functions. We conducted first randomized controlled trial to determine modulations brain activity associated with working memory (WM) training in adults attention‐deficit hyperactivity disorder (ADHD). At baseline, we assessed aberrant functional n‐back WM task comparing 44 ADHD 18 healthy controls using fMRI. Participants were then train on an adaptive...
Oncolytic immunotherapy with cytokine armed replication competent viruses is an emerging approach in cancer treatment. In a recent randomized trial, increase response rate was seen but the effect on overall survival not known any virus. To facilitate trials, we performed case-control study assessing of 270 patients treated Advanced Therapy Access Program (ATAP), comparison to matched concurrent controls from same hospital. The all virus increased over controls. However, when analysis...
After the landmark approval of T-VEC, oncolytic viruses are finding their way to clinics. However, response rates have still room for improvement, and unfortunately there currently no available markers predict responses immunotherapy. Interleukin 8 (IL-8) production is upregulated in many cancers it also connects several pathways that been shown impair efficacy adenoviral We studied role IL-8 103 cancer patients treated with adenoviruses. found high baseline serum concentration be...