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expert reaction to phase 1 trial of CRISPR-edited cells in patients with advanced cancer

Research, published in Science, reports on the first US clinical trial of CRISPR-edited cells in patients with advanced cancer.

 

Prof Justin Stebbing, NIHR Research Professor of Cancer Medicine and Medical Oncology, Imperial College London, said:

“By using new technologies that can change genes, it looks like we can now engineer immune cells outside the body to safely contribute to cancer treatment.  By modifying the DNA of these immune T cells, using an approach called CRISPR, it seemed to enhance both their cancer killing abilities and importantly their safety profile.

“This opens up new possibilities for immunotherapy using cells, so called cellular immunotherapy, in solid malignancies like breast, colon and lung cancer, not just leukemias or myeloma patients.

“However, as with all these sorts of early reports it requires confirmation in much larger studies.  The most important finding of the study is that these new engineered T cells don’t seem to trigger an immune response against them, which in turn could have led to lots of side effects.  Whether it works in a broader population remains to be seen.”

 

Dr Astero Klampatsa, Team Leader in Thoracic Oncology Immunotherapy at The Institute of Cancer Research, London, said:

“We’re seeing incredibly exciting developments in immunotherapy for cancer – including in cellular immunotherapies, like CAR-T therapy, where a patient’s own immune cells are edited to recognise and attack cancer.

“In a new study, scientists used an advanced gene-editing technique called CRISPR-Cas9 to delete three genes from patient T-cells that might play a role in limiting their ability to attack tumours, and then engineered them to specifically attack tumour cells.

“The researchers treated three patients with advanced cancer with their own engineered T-cells, causing no significant harmful side-effects – and importantly, the T-cells were taken up in their blood and were still there up to nine months after the initial treatment.

“The new clinical study suggests that CRISPR-Cas9 can successfully be used to optimise cellular immunotherapies to treat solid tumours – but the therapy will need to be tested in more patients to better understand the side-effects and the benefit of the engineered T-cells over time.”

 

Prof Waseem Qasim, NIHR NIHR Research Professor of Cell and Gene Therapy, UCL, said:

“The authors have set another milestone here by showing the feasibility of using CRISPR to edit human immune cells which have been engineered in the hope they might one day be a tool to help to fight cancer.  This trial provides safety data and the results suggest the change can be delivered to the cells without obvious side effects – but of course we need to see results from larger numbers of patients in order to determine how effective the treatment is.  These gene editing technologies are evolving rapidly and we can expect to see more trials using similar approaches.”

 

Dr Qianxin Wu, Staff Scientist at the Wellcome Sanger Institute, said:

“This the first human phase I trial on CRISPR engineered T cell therapy.  It is encouraging to notice that these three patients did not show rejection of Cas9 edited cells.  More importantly, the capability of simultaneously editing multiple genes really shows the great potential of CRISPR technology in engineered cell therapy.”

 

‘CRISPR-engineered T cells in patients with refractory cancer’ by Edward A. Stadtmauer et al. was published in Science at 19:00 UK time on Thursday 6 February 2020.

DOI: 10.1126/science.aba7365

 

Declared interests

Dr Astero Klampatsa: “No conflicts of interest.”

Prof Waseem Qasim: “I’m involved trials treating patients with TALEN genome edited T cells and have received research funding from Servier and Cellectis.  Have patents submitted for CRISPR modification of T cells and eligible for revenue share through UCLB in relation to engineered T cells.”

Dr Qianxin Wu: “No conflicts of interest.”

None others received.

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