CRISPR cancer trial success paves the way for personalized treatments

Good news! Amazing stuff! Cancer is history (soon)! This is just the beginning! Imagine what could possibly be achieved with higher dosages during the next trial!

"A small clinical trial has shown that researchers can use CRISPR gene editing to alter immune cells so that they will recognize mutated proteins specific to a person’s tumours. Those cells can then be safely set loose in the body to find and destroy their target.

It is the first attempt to combine two hot areas in cancer research: gene editing to create personalized treatments, and engineering immune cells called T cells so as to better target tumours. The approach was tested in 16 people with solid tumours, including in the breast and colon. ...

Each of the 16 participants received engineered T cells with up to three different targets. Afterwards, the edited cells were found circulating in their blood, and were present in higher concentrations than non-edited cells near tumours. One month after treatment, five of the participants experienced stable disease, meaning that their tumours had not grown. Only two people experienced side effects that were likely due to the activity of the edited T cells.

Although the efficacy of the treatment was low, the researchers used relatively small doses of T cells to establish the safety of the approach ..."

From the abstract:

"The T cell receptor (TCR) provides the fine specificity of T cells to recognize mutations in cancer cells. We developed a clinical-grade approach based on CRISPR/Cas9 non-viral precision genome editing to simultaneously knock-out the two endogenous TCR genes, TCRα (TRAC) and TCRβ (TRBC), and insert in the TRAC locus the two chains of a neoantigen-specific TCR (neoTCR), isolated from the patient’s own circulating T cells using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with refractory solid cancers received up to three distinct neoTCR-transgenic cell products, each expressing a patient-specific neoTCR, in a cell dose-escalation, first-in-human phase 1 clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome, and one grade 3 encephalitis. All had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease, and the other 11 had disease progression as best response on therapy. NeoTCR-transgenic T cells were detected in tumour biopsies post-infusion at frequencies higher than the native TCRs pre-infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs recognizing mutational neoantigens, the simultaneous knock-out of the endogenous TCR and knock-in of the neoTCRs using single-step, non-viral precision genome editing, the manufacturing of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene edited neoTCR T cell products, and the ability of the transgenic T cells to traffic to the patients’ tumours."

CRISPR cancer trial success paves the way for personalized treatments ‘Most complicated therapy ever’ tailors bespoke, genome-edited immune cells to attack tumors.

Non-viral precision T cell receptor replacement for personalized cell therapy (no public access)

The CRISPR–Cas9 complex (blue and yellow) can precisely cut DNA (red)