Most Read Articles
14 Feb 2020
The phase III CASTOR and POLLUX studies previously demonstrated benefit of daratumumab plus bortezomib and dexamethasone (DVd) or lenalidomide and dexamethasone (DRd) vs standard-of-care (SoC) Vd or Rd regimen in relapsed or refractory multiple myeloma (R/R MM). The latest efficacy and safety results after 4 years of follow-up from CASTOR and POLLUX were presented at the American Society of Hematology (ASH) 61st Meeting & Exposition 2019 held in Orlando, Florida, US.  
Dr. Roy Herbst, Dr. David Spigel, 6 days ago
The third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) osimertinib is a standard of care in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC). Results of the ADAURA study, presented at the American Society of Clinical Oncology 2020 Virtual Scientific Programme (ASCO 2020), support earlier use of osimertinib in the adjuvant setting, with superior disease-free survival (DFS) in patients who underwent complete resection of stage IB/II/IIIA EGFR-positive NSCLC. 
Prof. Mark Shackleton, 01 Apr 2020
In recent years, the focus on immuno-oncology has generated a wealth of compelling evidence supporting the use of immune checkpoint inhibitors – in particular those targeting the programmed death-ligand 1 (PD-L1) or PD-1 pathway. At the 8th Oncology Summit organized by the Hong Kong Society of Clinical Oncology, Professor Mark Shackleton of Alfred Health and Monash University, Australia, discussed recent advances in immunotherapy for the management of metastatic Merkel cell carcinoma (MCC) with a focus on the role of the PD-L1 inhibitor avelumab.  
Dr. Jason Butler, 01 Apr 2020
Proteasome inhibitors have become a cornerstone of therapy for multiple myeloma (MM). At the Hong Kong Society of Myeloma Annual Scientific Meeting 2019, Dr Jason Butler of the Icon Cancer Care & Royal Brisbane and Women’s Hospital, Brisbane, Australia, reviewed current evidence for the use of proteasome inhibitors in the management of relapsed/refractory MM (R/R MM), with a focus on the efficacy and safety profile of carfilzomib.

CRISPR-edited T-cell therapy feasible in NSCLC

Natalia Reoutova
29 May 2020

Results of the world’s first-in-human phase I clinical trial of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 PD-1–edited T cells, recently published in Nature Medicine, suggest therapy’s feasibility in refractory non-small-cell lung cancer (NSCLC), with no severe treatment-related adverse events (TRAEs).

The dose-escalation study, co-led by researchers from the Chinese University of Hong Kong (CUHK) and Sichuan University in Chengdu, China, assessed the feasibility and safety of CRISPR-Cas9 PD-1–edited T-cell therapy in 12 patients with cytologically confirmed stage IIIB or IV NSCLC who failed multiple prior lines of therapy. While 11 patients experienced grade 1/2 TRAEs, there were no grade 3 TRAEs or treatment-related deaths. [Nat Med 2020;26:732-740]

More frequent AEs included lymphopenia (n=3), fatigue (n=3), leukopenia (n=2), fever (n=2), arthralgia (n=2) and skin rash (n=2). “The severity of AEs appeared to be dose-independent,” noted the researchers.

“Among the 12 enrolled patients, the median progression-free survival [PFS] was 7.7 weeks [95 percent confidence interval (CI), 6.9 weeks to 8.5 weeks]. The median overall survival was 42.6 weeks [95 percent CI, 10.3 weeks to 74.9 weeks],” reported the researchers on the secondary endpoints. The 8-week disease control rate was 16.7 percent (95 percent CI, 2.1 percent to 48.4 percent).

“Binding of the T cell surface PD-1 [receptor] with its ligand, PD-L1, expressed on the surface of cancer cells prevents the immune system from killing cancer cells. Anti–PD-1 checkpoint inhibitors are currently the standard first-line therapy for advanced NSCLC. We are exploring the use of an alternative tool, the CRISPR technology, to edit T cells and to prevent the PD-1 receptors on the surface of T cells from functioning,” explained Professor Tony Mok from the Department of Clinical Oncology, CUHK.

In the study, mononuclear cells were isolated from 60–80 mL of peripheral blood before every treatment cycle by centrifugation. Approximately 5–10 × 106 cells were transfected by electroporation technology with the intended Cas9 and single-guide RNA plasmids targeting exon 2 of the PD-1 gene. After electroporation, the gene-edited cells were expanded ex vivo and re-infused as therapeutic T cells.

To monitor the risk of off-target mutations, whole-genome sequencing and next-generation sequencing were performed on genomic DNA isolated from edited T cells before infusion. “The median mutation frequency of all off-target sites was 0.05 percent [range, 0–0.25 percent], which was much lower than that of the on-target site frequency [median, 1.69 percent with PD-1; range, 0.03–11.08 percent],” noted the researchers.

In addition, in vivo tracking of edited T cells was performed in peripheral blood mononuclear cells (PBMCs) during and following therapy. Presence of the edited PD-1 gene in PBMCs, acting as a surrogate for gene-edited T cells, was detected in 11 of the 12 treated patients at multiple time points between 8 and 52 weeks from the first infusion. “Interestingly, one patient with durable disease control showed a persistent, moderate level of edited PD-1 genes in PBMCs,” highlighted the researchers.

“In summary, this study has demonstrated the safety and feasibility of CRISPR-Cas9 gene–edited T-cell therapy targeting the PD-1 gene in a cohort of patients with advanced lung cancer. There were limited off-target effects observed with this approach, and we have demonstrated CRISPR-based technology to be clinically feasible,” concluded the researchers.

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Most Read Articles
14 Feb 2020
The phase III CASTOR and POLLUX studies previously demonstrated benefit of daratumumab plus bortezomib and dexamethasone (DVd) or lenalidomide and dexamethasone (DRd) vs standard-of-care (SoC) Vd or Rd regimen in relapsed or refractory multiple myeloma (R/R MM). The latest efficacy and safety results after 4 years of follow-up from CASTOR and POLLUX were presented at the American Society of Hematology (ASH) 61st Meeting & Exposition 2019 held in Orlando, Florida, US.  
Dr. Roy Herbst, Dr. David Spigel, 6 days ago
The third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) osimertinib is a standard of care in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC). Results of the ADAURA study, presented at the American Society of Clinical Oncology 2020 Virtual Scientific Programme (ASCO 2020), support earlier use of osimertinib in the adjuvant setting, with superior disease-free survival (DFS) in patients who underwent complete resection of stage IB/II/IIIA EGFR-positive NSCLC. 
Prof. Mark Shackleton, 01 Apr 2020
In recent years, the focus on immuno-oncology has generated a wealth of compelling evidence supporting the use of immune checkpoint inhibitors – in particular those targeting the programmed death-ligand 1 (PD-L1) or PD-1 pathway. At the 8th Oncology Summit organized by the Hong Kong Society of Clinical Oncology, Professor Mark Shackleton of Alfred Health and Monash University, Australia, discussed recent advances in immunotherapy for the management of metastatic Merkel cell carcinoma (MCC) with a focus on the role of the PD-L1 inhibitor avelumab.  
Dr. Jason Butler, 01 Apr 2020
Proteasome inhibitors have become a cornerstone of therapy for multiple myeloma (MM). At the Hong Kong Society of Myeloma Annual Scientific Meeting 2019, Dr Jason Butler of the Icon Cancer Care & Royal Brisbane and Women’s Hospital, Brisbane, Australia, reviewed current evidence for the use of proteasome inhibitors in the management of relapsed/refractory MM (R/R MM), with a focus on the efficacy and safety profile of carfilzomib.