A5082990711- Virus-based gene therapy research
- CAR-T cell therapy research
- Bladder and Urothelial Cancer Treatments
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Research and Treatments
- Urinary and Genital Oncology Studies
- Global Cancer Incidence and Screening
- Renal cell carcinoma treatment
- Cancer Immunotherapy and Biomarkers
- Multiple and Secondary Primary Cancers
- Genetic factors in colorectal cancer
- Colorectal Cancer Screening and Detection
- Prostate Cancer Treatment and Research
- Head and Neck Cancer Studies
- Cancer Diagnosis and Treatment
- Testicular diseases and treatments
- Viral gastroenteritis research and epidemiology
- Pancreatic and Hepatic Oncology Research
- Cervical Cancer and HPV Research
- Urinary Bladder and Prostate Research
- Prostate Cancer Diagnosis and Treatment
- Esophageal Cancer Research and Treatment
- Cancer Genomics and Diagnostics
- Cholangiocarcinoma and Gallbladder Cancer Studies
Helsinki University Hospital
2011-2025
University of Helsinki
2015-2024
University Health Network
2020-2023
John Wiley & Sons (United States)
2023
Hudson Institute
2023
University of Toronto
2020-2022
Princess Margaret Cancer Centre
2020-2022
Gene Therapy Laboratory
2021
Kymenlaakson keskussairaala
2016
Kotka Maritime Research Centre
2015
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...
Twenty-five patients with chemotherapy refractory cancer were treated a fully serotype 3-based oncolytic adenovirus Ad3-hTERT-E1A. In mice, Ad3 induced higher amounts of cytokines but less liver damage than Ad5 or Ad5/3. humans, the only grade 3 adverse reactions self-limiting cytopenias and generally safety profile resembled Ad5-based viruses. Patients that had been previously viruses presented longer lasting lymphocytopenia no median increase in Ad3-specific T-cells blood, suggesting...
// 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...
Cytokines have proven to be effective for cancer therapy, however whilst low-dose monotherapy with cytokines provides limited therapeutic benefit, high-dose treatment can lead a number of adverse events. Interleukin 7 has shown promising results in clinical trials, but anti-cancer effect was limited, part due low concentration the cytokine within tumor. We hypothesized that arming an oncolytic adenovirus 7, enabling high expression localized tumor microenvironment, would overcome systemic...
Oncolytic adenoviruses are an emerging experimental approach for treatment of tumors refractory to available modalities. Although preclinical results have been promising, and clinical safety has excellent, it is also apparent that can become virus resistant. The resistance mechanisms acquired by advanced against conventional therapies increasingly well understood, which allowed development countermeasures. To study this in the context oncolytic adenovirus, we developed two vivo models...
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...
Lung cancer remains among the most difficult-to-treat malignancies and is leading cause of cancer-related deaths worldwide. The introduction targeted therapies checkpoint inhibitors has improved treatment outcomes; however, patients with advanced-stage non-small cell lung (NSCLC) eventually fail these therapies. Therefore, there a major unmet clinical need for refractory/resistant NSCLC. Here, we tested combination aPD-1 adenovirus armed TNFα IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent...
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...
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,...
Dendritic cells (DCs) are crucial players in promoting immune responses. Logically, adoptive DC therapy is a promising approach cancer immunotherapy. One of the major obstacles immunotherapy general immunosuppressive tumor microenvironment, which hampers maturation and activation DCs. Therefore, human clinical outcomes with alone have been disappointing. In this study, we use fully serotype 3 oncolytic adenovirus Ad3-hTERT-CMV-hCD40L, expressing CD40L, to modulate microenvironment...
Cancers of the head and neck (HN) are heterogeneous tumors with incidence rates varying globally. In Northern Europe oral oropharyngeal cancers most common individual types. Survival for HN varies by tumor type but them survival trends not well known over extended periods time.
Vaccination with dendritic cells (DCs), the most potent professional antigen-presenting in body, is a promising approach cancer immunotherapy. However, tumors induce immunosuppression their microenvironment that suppresses and impairs function of DCs. Therefore, human clinical trials DC therapy have often been disappointing. To improve therapeutic efficacy to overcome major obstacles therapy, we generated novel adenovirus, Ad3-hTERT-CMV-hCD40L, which fully serotype 3 expresses hCD40L for...
Checkpoint inhibitors have revolutionized cancer therapy and validated immunotherapy as an approach. Unfortunately, responses are seen in a minority of patients. Our objective is to use engineered adenoviruses designed increase lymphocyte trafficking cytokine production at the tumor, assess if they response rate checkpoint inhibition, these features been regarded predictive for responses. When Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (an oncolytic adenovirus coding TNFa IL-2, also known TILT-123) were...
Oncolytic viruses are a potent form of active immunotherapy, capable invoking antitumor T-cell responses. Meanwhile, less is known about their effects on immune checkpoints, the main targets for passive immunotherapy cancer. immunoglobulin and mucin domain-3 (TIM-3) coinhibitory checkpoint driving exhaustion in Here we investigated oncolytic adenovirus TIM-3 tumor-infiltrating cells clinical impact patients with cancer receiving immunotherapy.Modulation expression was studied preclinically...
Cancers of the oral cavity and pharynx encompass a heterogeneous group cancers for which known risk factors include smoking, alcohol consumption human papilloma virus (HPV) infection but their influence is site-specific with HPV mainly influencing oropharyngeal cancer. Their incidence survival rates are not well over extended periods time.Data were obtained Finnish (FI) Swedish (SE) patients from Nordcan database recently updated through 2019. Age-adjusted trends (FI 1953, SE 1960) relative...
T cell-focused cancer immunotherapy including checkpoint inhibitors and cell therapies has been rapidly evolving over the past decade. Nevertheless, there remains a major unmet medical need in oncology generally immuno-oncology specifically. We have constructed an oncolytic adenovirus, Ad5/3-E2F-d24-aMUC1aCD3-IL-2 (TILT-322), which is armed with human aMUC1aCD3 engager IL-2. TILT-322 treatment stimulated cytotoxicity through increased presence of granzyme B, perforin, interferon-gamma....
We analysed cancer risks in patients with urinary tract stones but some features of the generated results alarmed us about possible surveillance bias, which we describe this report. used nationwide Swedish hospital records to identify (N = 211,718) and registration data for years 1987 2012. Standardized incidence ratios (SIRs) were calculated after last medical contact stones. All cancers increased kidney (SIR 1.54, 95%CI: 1.50-1.58), ureter (1.44, 1.42-1.47), mixed (1.51, 1.44-1.58) bladder...