Reacción a "Reactions to clinical trial using CRISPR to modify patient's own T lymphocytes for cancer treatment"

This is a great study, seminal and of excellent quality. It is a pioneering work because of the technology applied to modify these lymphocytes and make these TCRs [T lymphocyte receptors] using CRISPR/Cas9 gene editing technology instead of viral vectors, which are always more complex, and because of the biological proof of concept demonstrated in tumor biopsies, with the presence of these modified lymphocytes with NeoTCRs in the tumor. In addition, the authors silenced (knock-out) their own TCRs (alpha and beta) and constructed the new specific one (neoTCR) to give it greater selectivity and specificity. The study opens the door to a new way to modify lymphocyte TCRs and to select the neoantigens [targets present only in tumor cells] toward which these TCRs are directed by means of a bioinformatics algorithm, in a more efficient way. 

This is a very important step in the field of adoptive cell therapy with modified lymphocytes (NeoTCRs) to help more and more patients with solid tumors to benefit from these treatments. Until now, the different cellular immunotherapy technologies have mainly focused on patients with hematological tumors. For the time being, antitumor activity is modest, but it is a clear proof of concept to be improved in the future. 

As for the limitations, the authors are very elegant in clearly showing the complexity of the process and the limitations of the technology. Of 187 initial patients who sign the consent form, only 16 patients are ultimately able to be treated. Many of these complexities and limitations are very amenable to future improvements in patient enrichment and selection (less advanced disease and access to tumor samples with better tumor content) and improved technology.