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New CART cell therapy shows promising early results in children with neuroblastoma

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New CAR T cells Therapies developed by UCL researchers and designed to target cancerous tumors show promising early results in children with neuroblastoma, a rare form of childhood cancer.

For this principle empirical study, researchers at UCL Great Ormond Street Child Health Institute (GOS ICH) and UCL Cancer Institute have modified, recognized, and killed patients’ own T cells (a type of immune cell). I made it possible. Neuroblastoma Tumor cells.

Twelve children with relapsed or refractory (disease does not respond to treatment) neuroblastoma were treated as part of a Phase I clinical trial funded by Cancer Research UK.

Research published in Scientific translation medicineIs one of the first studies to demonstrate CAR T cells that achieve rapid regression against solid tumors (non-hematological cancers). Although the beneficial effects lasted only for a short period of time, this study provides important evidence that this particular CART cell therapy can be used as a future treatment for children with solid tumors.

Neuroblastoma is a rare type of cancer that mainly affects infants and young children and arises from specialized nerve cells (neuroblastomas) that are left out of the baby’s development in the womb.

Up to 100 children are diagnosed with neuroblastoma each year in the UK. Current treatments for children with advanced type neuroblastoma include surgical resection, chemotherapy with stem cell transplantation, radiation therapy, and antibody therapy. Despite this intensive treatment, long-term survival is 50-60 percent.

In CAR T cell therapy, a type of immunotherapy, T cells are designed to contain a molecule called a chimeric antigen receptor (CAR) that can specifically recognize cancer cells.

In this study, patients’ own T cells were modified with CAR to target GD2 surface proteins, which are very abundant in almost all neuroblastoma cells but found at very low levels in healthy cells. did.

Researchers have found that with a sufficient amount of modified CAR T cells, this treatment rapidly reduces the tumor size in some treated patients. These effects were temporary. Importantly, in all patients, CAR T cells did not cause harmful side effects on healthy tissues expressing the GD2 molecule.

Dr. Karin Straathof, a research group leader at UCL GOS ICH and a pediatric oncologist at the Great Ormond Street Hospital NHS Trust, said: “This study shows the antitumor activity induced by these modified T cells.

“Although the antitumor activity seen was transient, it provides an important proof of principle that CAR T cells directed to the GD2 molecule can be used for solid tumors in children.

“High-risk neuroblastoma requires new treatments, and more research hopes to develop them into treatments that provide a more lasting response and increase the number of patients who can be cured. . “

Targeting solid tumors by CAR T cells depends on their infiltration and spread within the tumor microenvironment, and therefore far fewer clinical responses have been reported.

Rapid regression of neuroblastoma cells is promising, especially as this activity was observed in the absence of neurotoxicity that occurs with antibody-based approaches that target GD2. “

Dr. Martin Pule, Senior Author of UCL Cancer Institute

“Targeting neuroblastoma with GD2 CAR T cells seems to be an effective and safe strategy, but further modifications are needed to extend the lifespan of CAR T cells,” Dr. Pule added.

Dr. Sue Brook, Medical Advisor at Cancer Research UK, said: “Children who have difficulty treating cancer, such as neuroblastoma, have limited treatment options, especially if the cancer has recurred.

“The initial results of GD2CAR-T treatment look promising, especially with early safety data, but more work is needed to prolong the response and look forward to the next step in its development. I am. “

The research team is working with Autolus, a clinical biopharmacy company developing next-generation programmed T cell therapies for cancer treatment, to prepare for the next clinical study. This study evaluates AUTO6NG built on this approach, which utilizes the same GD2CAR and additional programming modules designed to extend. Effectiveness And persistence.

Source:

Journal reference:

Straathof, K. , et al. (2020) On-target off of GD2 chimeric antigen receptor T cells in patients with neuroblastoma Non-tumor antitumor activity. Scientific translation medicine. doi.org/10.1126/scitranslmed.abd6169..

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