New CRISPR cell therapy overcomes first hurdle in trial

Written by Alexander Marshall

A new CRISPR-based, autologous transplant therapy is reporting safe preliminary results.

A new autologous transplant trial conducted by a team at The University of Pennsylvania (PA, USA) has reported positive initial results. The regime, involving the genetic editing of a patient’s cells through CRISPR technology, is being tested in two patients with multiple myeloma and one patient with a sarcoma in the hopes that the engineered T-cells can be utilized to combat cancer. Edward Stadtmauer (University of Pennsylvania), the principal investigator of the project, plans to present his findings at the 61st American Society of Hematology Annual Meeting (7—10 December 2019; FL, USA).

In a manner reminiscent of CAR-T therapy, T-cells were removed from patients undergoing cancer treatment and edited. The cells were then transplanted back into the patients following a short course of chemotherapy. Both the FDA and NIH have approved the trial and initial results suggest that the cells have successfully engrafted into the patients, expanded, and bound to cancerous cells, without any apparent side effects. However, so far patients have not responded to the treatment and it is unknown how effective the edited cells will be.

Editing the T-cells has been simplified by the utilization of CRISPR technology, which has allowed the knockout of three genes within the cells: two natural receptors and the well-characterized immune system repressor, PD1. A high-affinity T-cell-receptor, which is specifically designed to target the cancerous NY-ESO-1 antigen, is then inserted into the modified cells using a lentivirus before they are transplanted.

The aim of this procedure is to enhance the effectiveness of a patient’s immune system to target cancerous cells; although, at this stage the researchers’ primary focus is to confirm an ability to produce genetically edited, functioning, transplantable T-cells.

         Our use of CRISPR editing is geared toward improving the effectiveness of gene therapies, not editing a patient’s DNA,” commented the study’s senior author, Professor Carl June (University of Pennsylvania).

It is hoped that by targeting PD1, which is known to enable tumors to evade the immune system, and inserting the enhanced T-cell-receptor, the T-cells will be more effective in their targeting of cancerous cells. Unfortunately, the cells are not naturally active and require the expression of HLA-A201 in subjects, limiting the procedure to only a subset of patients.


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