Update: CRISPR'd T cells to Treat Myeloma, Melanoma and Other Skin Cancers


A phase 1 human clinical trial has commenced at the University of Pennsylvania, in which gene editing will be used in individuals with Myeloma, Melanoma and other skin cancers.


Specifically, NYCE T cells will be removed from the patients and transduced with a lentiviral vector to initiate the expression of the NY-ESO-1 receptor. NY-ESO-1 also known as New York esophageal squamous cell carcinoma 1 is a cancer antigen found on many cancerous tumour types but with varying expression levels. NY-ESO-1 is able to activate a host immune response, therefore, introducing an NY-ESO-1 receptor in immune cells would redirect the immune cells towards tumour cells specifically expressing NY-ESO-1.


Furthermore, in the study, the T cells will also be electroporated with CRISPR gRNA to inhibit the expression of TCRα, TCRβ, and PD-1. PD-1 along with other molecules are used to regulate the immune response by reducing T cell proliferation. In cancer, the immune response to tumour cells is suppressed. Therefore, inhibition of the PD-1 checkpoint in conjunction with the NY-ESO-1 receptor could be an efficient therapy for cancer.


The aims of the study were to determine the safety of the edited T cells, the sustainability of manufacturing the T cells and to assess the overall patient survival.

Update

A statement was released on Penn Medicine News, discussing the preliminary results from this clinical trial.


Three individuals have had the treatment administered, it seems that the CRISPR edited cells are safe as there were no severe adverse reactions in the patients due to the treatment. It was also reported that the CRISPR edited T cells were able to divide and bind to the target. However, so far none of the patients have had a complete response to the therapy.


The patient response will need to be monitored over a longer period of time to determine the effectiveness of the treatment, but it is likely that the therapy will need to be optimised. As for now, the patients will continue to be monitored.


Reference:

1.https://www.pennmedicine.org/news/news-releases/2019/november/results-first-us-trial-crispr-edited-immune-cells-cancer-patients-safety-of-approach

2.https://clinicaltrials.gov/ct2/show/NCT03399448?cond=CRISPR&rank=2 3.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941317/



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