Bruce Levine, PhD, research associate professor at the Perelman School of Medicine, and facility director, Clinical Cell and Vaccine Production Facility at Penn's Abramson Cancer Center, shares some of the response to the findings of "serial killer" T cells to treat cancer.
Our recent breakthrough in using genetically modified T cells to destroy cancer cells announced continues to draw attention nationally and around the world.
The research, published simultaneously in the New England Journal of Medicine (NEJM) and Science Translational Medicine in August, is the first demonstration of the use of gene transfer therapy to create "serial killer" T cells aimed at cancerous tumors. The study shows sustained remissions of up to a year among a small group of patients with advanced chronic lymphocytic leukemia (CLL) treated with genetically engineered versions of their own T cells.
Each of our recent reports were selected and evaluated by the Faculty of 1000 (F1000). F1000 identifies and evaluates the most important articles in biology and medical research publications. Articles are selected by a peer-nominated global 'faculty' of the world's leading scientists and clinicians who then rate them and explain their importance. On average, 1,500 new evaluations are published each month; representing approximately 2 percent of all published articles in the biological and medical sciences.
The comments from the F1000 evaluators follow. While the evaluations highlight the technical research, both evaluations rated the study as "exceptional."
Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. (N Engl J Med 2011 Aug 10), evaluated by Christopher Thanos.
Evaluation details: Exceptional [10] New Finding, Technique
Review: This exceptional article investigated a possible avenue for the treatment of chronic lymphoid leukemia (CLL). The authors used a lentivirus system to infect harvested T cells with a vector that expresses a chimeric protein consisting of an extracellular, anti-CD19 scFv fused to intracellular CD137 and CD3 signalling domains. T cells expressing this chimeric anti-CD19-CD137-CD3 fusion protein were then administered back to a CLL patient and the results were profound. There was massive proliferation of these engineered T cells (>1000X) after administration to the patient, and, by day 23, there was no evidence of CLL in the patient's bone marrow (complete remission).
T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. (Sci Transl Med 2011 Aug 10), evaluated by Joyce Solheim.
Evaluation details: Exceptional [10] Clinical Trial
Review: This article expands on exciting new developments in the use of genetically modified T cells expressing antibody-binding domains as therapies against malignancies. As an accompaniment to their recent case report in the New England Journal of Medicine on the amazing impact of T cells expressing a CD19-specific chimeric antigen receptor, the authors have here provided a more detailed analysis. In this article, they describe the expansion and trafficking of the T cells that they have used to target chronic lymphocytic leukemia, and they delineate the immune responses (including the establishment of T cell memory and prolonged effector function). The clinical effects noted by the authors were impressive in all three patients, although the side effects observed were also quite significant. The specific strategies used by these investigators in their production of the modified T cells have yielded new clues about how complex immune responses in humans can be driven, and have surely laid the groundwork for many future clinical trials, particularly for B cell malignancies.
Senior author of the NEJM paper is Carl June, MD, director of translational research and professor of pathology and laboratory medicine at the Abramson Cancer Center, who led the work. Co-principal investigator is David Porter, MD, professor of medicine and director of Blood and Marrow Transplantation. Co-authors include Bruce Levine, PhD; Michael Kalos, PhD, and Adam Bagg, MD; all from Penn Medicine.
Drs. Kalos and Levine are co-first authors on the Science Translational Medicine paper. Other co-authors include Drs. June, Porter and Bagg and Sharyn Katz, MD, from Penn and Stephan Grupp, MD, PhD, Children's Hospital of Philadelphia.
Our recent breakthrough in using genetically modified T cells to destroy cancer cells announced continues to draw attention nationally and around the world.
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| Genetically modified T cells |
Each of our recent reports were selected and evaluated by the Faculty of 1000 (F1000). F1000 identifies and evaluates the most important articles in biology and medical research publications. Articles are selected by a peer-nominated global 'faculty' of the world's leading scientists and clinicians who then rate them and explain their importance. On average, 1,500 new evaluations are published each month; representing approximately 2 percent of all published articles in the biological and medical sciences.
The comments from the F1000 evaluators follow. While the evaluations highlight the technical research, both evaluations rated the study as "exceptional."
Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. (N Engl J Med 2011 Aug 10), evaluated by Christopher Thanos.
Evaluation details: Exceptional [10] New Finding, Technique
Review: This exceptional article investigated a possible avenue for the treatment of chronic lymphoid leukemia (CLL). The authors used a lentivirus system to infect harvested T cells with a vector that expresses a chimeric protein consisting of an extracellular, anti-CD19 scFv fused to intracellular CD137 and CD3 signalling domains. T cells expressing this chimeric anti-CD19-CD137-CD3 fusion protein were then administered back to a CLL patient and the results were profound. There was massive proliferation of these engineered T cells (>1000X) after administration to the patient, and, by day 23, there was no evidence of CLL in the patient's bone marrow (complete remission).
T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. (Sci Transl Med 2011 Aug 10), evaluated by Joyce Solheim.
Evaluation details: Exceptional [10] Clinical Trial
Review: This article expands on exciting new developments in the use of genetically modified T cells expressing antibody-binding domains as therapies against malignancies. As an accompaniment to their recent case report in the New England Journal of Medicine on the amazing impact of T cells expressing a CD19-specific chimeric antigen receptor, the authors have here provided a more detailed analysis. In this article, they describe the expansion and trafficking of the T cells that they have used to target chronic lymphocytic leukemia, and they delineate the immune responses (including the establishment of T cell memory and prolonged effector function). The clinical effects noted by the authors were impressive in all three patients, although the side effects observed were also quite significant. The specific strategies used by these investigators in their production of the modified T cells have yielded new clues about how complex immune responses in humans can be driven, and have surely laid the groundwork for many future clinical trials, particularly for B cell malignancies.
Senior author of the NEJM paper is Carl June, MD, director of translational research and professor of pathology and laboratory medicine at the Abramson Cancer Center, who led the work. Co-principal investigator is David Porter, MD, professor of medicine and director of Blood and Marrow Transplantation. Co-authors include Bruce Levine, PhD; Michael Kalos, PhD, and Adam Bagg, MD; all from Penn Medicine.
Drs. Kalos and Levine are co-first authors on the Science Translational Medicine paper. Other co-authors include Drs. June, Porter and Bagg and Sharyn Katz, MD, from Penn and Stephan Grupp, MD, PhD, Children's Hospital of Philadelphia.
