Personalized immunotherapy for cancer patients shows promise

November 2022 Cancer trials Nalinee Pandey

Researchers have edited patients’ immune cells and altered them to target a person’s tumours. The encouraging findings of this CRISPR cancer trial were recently published in the Journal Nature.

A team of researchers at the University of California, Los Angeles and PACT pharma in South San Francisco (USA) has developed a complex approach of isolating patient-specific T Cells, engineering them with CRISPR-based gene editing and injecting these edited T-cells back into the patient now enabled to recognise tumour-specific mutations and hence attack person’s tumour cells.

A small clinical trial was conducted to study the efficacy and safety of CRISPR gene editing of personalised T cells. The phase 1a study enrolled 16 patients (median age=47 years) with either colorectal cancer (n=11), breast cancer (n=2), ovarian cancer (n=1), melanoma (n=1), or non-small cell lung carcinoma (n=1).  DNA was isolated and sequenced from each patient’s blood and tumour biopsies and analysed to predict mutations with a high likelihood of generating a response from T cells. Next, blood samples were taken from each participant and edited to insert T-cell receptors (TCR) capable of recognizing patient-specific mutational neo-antigens. Finally, each participant received engineered T cells specific to three different targets.

Different numbers of edited TCRs were found circulating in the blood of the participants (1 TCR in four patients, 2 TCR in three and 3 TCRs in nine patients). After treatment of one month, five patients had stable disease, and the remaining eleven had progressive disease. Treatment-related side effects were seen in only two patients. 

The proof of concept study shows the efficacy and safety of the treatment. Also, these findings will pave the way for future studies with modified protocols and escalated doses of T cells.

References

  1. Foy SP, Jacoby K, Bota DA, et al. Non-viral T cell receptor replacement for personalized cell therapy. Nature. Published online November 10, 2022.
  2. Ledford H. CRISPR cancer trial success paves the way for personalized treatments. Nature. 2022 Nov;611(7936):433-434.
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