CRISPR Clinical Trial Update

This week we focus on two Phase 1/2 trials sponsored by The First Affiliated Hospital of Guangdong Pharmaceutical University (China) in partnership with Guangzhou Anjie Biomedical Technology Co., Ltd. (China) and University of Technology, Sydney (Australia).

The first trial will evaluate a combined vaccine/CRISPR-edited T cell therapy for prostate cancer, and the second will evaluate a CRISPR-edited CAR-T cell therapy for non-small cell lung cancer (NSCLC).

Combined cancer vaccine and CRISPR-edited T cells for prostate cancer

This trial will evaluate the safety and efficacy of a combination therapy for prostate cancer in three patient subgroups (or study arms). The experimental group will receive combination treatment with a prostate cancer vaccine and PD-1 knockout T cells. The other two groups are active comparator groups, where one will receive the vaccine as monotherapy and the other will receive the PD-1 knockout T cells as monotherapy.

The cancer vaccine is custom-prepared ex vivo using patient-isolated peripheral blood mononuclear cells (PBMCs). The cells are isolated and cultured with a recombinant fusion protein PAP-GM-CSF, which consists of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF).

PAP is overexpressed in 95 % of prostate cancer tissues and is an attractive target for the development of anti-prostate tumour vaccines within the immunotherapy field. GM-CSF is an immune stimulant that promotes the maturation of PBMCs to dendritic cells, which can then mount an anti-tumour response against cancer cells expressing PAP.

The PD-1 gene encodes the PD-1 protein that functions as a safety switch on T cells that cancer cells exploit to evade T cell-mediated immune responses. PD-1 disruption is sometimes used in CAR T-cell development to enhance anti-tumour activity. The PD-1 knockout engineered T cells are also prepared using patients’ own T cells and the PD-1 gene is knocked out using CRISPR-Cas9 technology.

This trial, which is currently in the recruitment stage, aims to enrol a total of 30 adult males. Each participant will receive either the therapeutic vaccine and/or PD-1 knockout T cells a total of three times over a 2-week period. Primary and secondary outcome measures include an assessment of adverse events and response rate and survival, respectively.

The estimated study completion date is August 2021.