10 Questions
What is the primary target of the chimeric antigen receptor (CAR) T-cell therapy mentioned in the article?
CD19
What is a potential advantage of using natural killer (NK) cells modified to express an anti-CD19 CAR?
Overcoming the limitations of CAR T-cell therapy, including toxic effects and complex manufacturing processes.
What is the affiliation of the authors of the article, Drs. Liu, Marin, and Banerjee?
University of Texas M.D. Anderson Cancer Center, Houston
What is the DOI of the article, which was updated on February 7, 2020?
10.1056/NEJMoa1910607
What is the title of the journal in which the article was published?
The New England Journal of Medicine
What was the purpose of administering lymphodepleting chemotherapy to patients before infusing CAR-NK cells?
To prepare the body for the infusion of CAR-NK cells
What was the primary goal of using inducible caspase 9 as a safety switch in the CAR-NK cells?
To allow for the elimination of CAR-NK cells if toxic effects occur
What was the response rate among the 11 patients treated with CAR-NK cells?
73% (8 out of 11 patients had a response)
How long did the infused CAR-NK cells persist in the body?
At least 12 months
What was the primary toxicity concern that was NOT associated with the administration of CAR-NK cells?
Cytokine release syndrome, neurotoxicity, or graft-versus-host disease
Study Notes
Background of CAR-T Cell Therapy
- Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers
- However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex
- Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations
Phase 1 and 2 Trial of CAR-NK Cells
- 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkin's lymphoma or chronic lymphocytic leukemia [CLL]) received HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood
- NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch
- The cells were expanded ex vivo and administered in a single infusion at one of three doses (1×10^5, 1×10^6, or 1×10^7 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy
Results of the Trial
- The administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease
- There was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline
- The maximum tolerated dose was not reached
- 8 out of 11 patients (73%) had a response, with 7 patients achieving complete remission and 1 patient having remission of the Richter's transformation component but persisting with CLL
- Responses were rapid and seen within 30 days after infusion at all dose levels
- The infused CAR-NK cells expanded and persisted at low levels for at least 12 months
Test your knowledge on a medical journal article discussing stem cell transplantation, leukemia, and lymphoma from the University of Texas M.D. Anderson Cancer Center. Assess your understanding of the research and its findings.
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