Study Opens the Way for a Potential New Cure for Children with Hard-to-Treat Neuroblastoma

AHA Publisher — Mon, 11 Jan 2021 08:00:58 +0000

University of Gothenburg via News-Medical Net – Researchers at the University of Gothenburg now suggest a possible cure for children with hard-to-treat forms of neuroblastoma using a new combination of drugs. In a new study in the journal Cancer Research, they describe how a two small molecule-based drug combination likely inhibit the tumor’s growth. Neuroblastoma is the most common form of childhood cancer, derived from the peripheral nervous system, i.e., the part of the nervous system that is not the brain or spinal cord. The disease can occur in the chest, neck, abdomen and adrenal glands and can also spread to the spine. Symptoms include general aches, anemia and skeletal pain. The average age of children at diagnosis is 17 months, and it is rarely diagnosed over the age of five. The milder form of neuroblastoma can, in some cases, self-heal, while the more aggressive form is the deadliest form of childhood cancer. Treatment is successful in less than half of these cases. A Long Noncoding RNA Molecule Influences Tumor Suppressor Gene Expression Central molecule in the study is the p53 gene. The p53 gene is often mutated in other cancer forms but rarely in neuroblastoma. When it is not mutated, p53 codes for a protein that inhibit the growth of cancer. This study shows that how the expression levels of a long non-coding RNA molecule influences the function of p53 protein. Interestingly, this long non-coding RNA increases p53 function in the nucleus to make tumor cells more susceptible to cytostatic treatment.” (Chandrasekhar Kanduri, Professor, Medical genetics specialized in RNA epigenetics, University of Gothenburg) Two Small Molecule-Based Drug Combination for Neuroblastoma The RNA molecule NBAT1 changes the function of the protein CRM1, which transports p53 from nucleus to cytoplasm. NBAT1 also helps in keeping the p53 protein in the nucleus to increase p53 controlled gene expression. Based on these findings, the research group tested a new treatment that combines the drugs Selinexor and Nutlin-3a. Both drugs are currently undergoing clinical trials for cancer treatments but not for neuroblastoma. Selinexor restores p53’s ability to inhibit cancer growth and Nutlin-3a inhibits the breakdown of p53. “The combination treatment blocks the protein export function of CRM1, which leads to p53 accumulation in the cell nucleus. This treatment increases p53 dependent functions, such as DNA damage and cell death. We think that combining these two drugs with current treatment strategies may allow us to cure hard-to-treat neuroblastomas.” The results are promising, but they are based on preclinical studies of cancer cell lines and mouse models (xenografts) and more research is needed before the findings can be translated into treatment. These laboratory results have been partly validated with the neuroblastoma patient data, obtained in collaboration with the researchers at Karolinska Institutet. Thus, this study has clearly opened the way for a potential new treatment strategy for high-risk neuroblastoma patients. To read the original article click here.

The post Study Opens the Way for a Potential New Cure for Children with Hard-to-Treat Neuroblastoma appeared first on Amazing Health Advances.

New Immunotherapy Shows Promise Against Rare Childhood Cancer

AHA Publisher — Mon, 30 Nov 2020 08:00:55 +0000

University College London via EurekAlert – A novel CAR T-cell therapy developed by researchers at UCL and designed to target cancerous tumours, has shown promising early results in children with neuroblastoma, a rare form of childhood cancer. For this proof-of-principle study, researchers at the UCL Great Ormond Street Institute for Child Health (GOS ICH) and the UCL Cancer Institute modified the patient’s own T-cells (a type of immune cell), equipping them to recognise and kill neuroblastoma tumour cells. Twelve children with relapsed or refractory (where the disease does not respond to treatment) neuroblastoma were treated as part of the Cancer Research UK-funded phase I clinical trial. The research, published in Science Translational Medicine, is one of the first studies to demonstrate CAR T-cells achieving rapid regression against a solid cancer (non-blood cancer). Although the beneficial effects only lasted a short while, the study provides important evidence that this specific CAR T-cell treatment could be used as a future treatment for children with solid cancers. Neuroblastoma is a rare type of cancer that mostly affects babies and young children and develops from specialised nerve cells (neuroblasts) left behind from a baby’s development in the womb. Up to 100 children in the UK are diagnosed with neuroblastoma each year. Current treatment for children with an aggressive type of neuroblastoma includes surgical removal, chemotherapy with stem-cell transplant, radiotherapy and antibody therapy. Despite this intensive treatment long-term survival is between 50-60 per cent. In CAR T-cell therapy, a type of immunotherapy, T-cells are engineered to contain a molecule called a chimeric antigen receptor (CAR) on their surface which can specifically recognise cancerous cells. For this study the patients’ own T-cells were modified with a CAR to target the GD2 surface protein, which is highly abundant on almost all neuroblastoma cells, but found at very low levels in healthy cells. Researchers found that when using a sufficient dose* of the modified CAR T-cells, this treatment induced rapid reduction in tumour size in some of the patients treated. These effects were transient. Importantly, in all patients the CAR T-cells did not cause any harmful side effects in healthy tissues that express the GD2 molecule. Lead author, Dr Karin Straathof, Research group leader at UCL GOS ICH and Consultant Paediatric Oncologist at Great Ormond Street Hospital NHS Trust said: “It’s encouraging to see the anti-tumour activity induced by these modified T-cells in some of the patients on this study. “While the anti-tumour activity seen was only transient, it provides an important proof-of-principle that CAR T-cells directed at the GD2 molecule could be used against solid cancers in children. “New treatments are needed for high-risk neuroblastoma and with more research we hope to develop this further into a treatment that results in lasting responses and increases the number of patients that can be cured.” Senior author, Dr Martin Pule (UCL Cancer Institute) said: “Targeting of solid cancers by CAR T-cells is dependent on their infiltration and expansion within the tumour microenvironment, and thus far fewer clinical responses have been reported. “The rapid regression in neuroblastoma cells is promising, particularly as this activity was observed in the absence of neurotoxicity which occurs with antibody-based approaches that target GD2.” Dr Pule added: “Targeting neuroblastoma with GD2 CAR T-cells appears to be a valid and safe strategy but requires further modification to promote CAR T-cell longevity.” Dr Sue Brook, medical advisor at Cancer Research UK, said: “Children who have hard to treat cancers like neuroblastoma have limited treatment options open to them, especially when the cancer returns. “The early results for the GD2 CAR-T treatment look promising, especially due to the initial safety data. However more work is needed on making the response last longer, and we are looking forward to seeing the next steps in its development.” The research team are preparing for their next clinical study in collaboration with Autolus, a clinical-stage biopharmaceutical company developing next-generation, programmed T-cell therapies for the treatment of cancer. This study will evaluate AUTO6NG, which builds on this approach utilising the same GD2 CAR alongside additional programming modules designed to enhance efficacy and persistence. To read the original article click here.

The post New Immunotherapy Shows Promise Against Rare Childhood Cancer appeared first on Amazing Health Advances.

neuroblastoma Archives - Amazing Health Advances

Study Opens the Way for a Potential New Cure for Children with Hard-to-Treat Neuroblastoma

New Immunotherapy Shows Promise Against Rare Childhood Cancer