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Medical New Cancer Treatment

  1. Sep 13, 2011 #1

    LeonhardEuler

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    Gold Member

    I just read this article in the New York Times, and I'm surprised it's not bigger news considering how important it could be if the treatment turns out to be as effective as it seems:
    http://www.nytimes.com/2011/09/13/health/13gene.html?pagewanted=1&_r=2

    Later they mention it giving the same result on a second patient and a partial remission in a third, and they also talk about how it could be applied to many other forms of cancer. This seems like really good news to me, but I don't know that much about it. I'm curious about what people think of the prospects of this working out.
     
  2. jcsd
  3. Sep 14, 2011 #2
    Very interesting. It seems there might be a risk of it killing you before it cures you, though.
     
  4. Sep 14, 2011 #3

    Ryan_m_b

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    Staff: Mentor

    The research has been published as two papers. Here are the abstracts;

    Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia
    David L. Porter, M.D., Bruce L. Levine, Ph.D., Michael Kalos, Ph.D., Adam Bagg, M.D., and Carl H. June, M.D.
    N Engl J Med 2011; 365:725-733
    http://www.nejm.org/doi/full/10.1056/NEJMoa1103849

    We designed a lentiviral vector expressing a chimeric antigen receptor with specificity for the B-cell antigen CD19, coupled with CD137 (a costimulatory receptor in T cells [4-1BB]) and CD3-zeta (a signal-transduction component of the T-cell antigen receptor) signaling domains. A low dose (approximately 1.5×105 cells per kilogram of body weight) of autologous chimeric antigen receptor–modified T cells reinfused into a patient with refractory chronic lymphocytic leukemia (CLL) expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo, with delayed development of the tumor lysis syndrome and with complete remission. Apart from the tumor lysis syndrome, the only other grade 3/4 toxic effect related to chimeric antigen receptor T cells was lymphopenia. Engineered cells persisted at high levels for 6 months in the blood and bone marrow and continued to express the chimeric antigen receptor. A specific immune response was detected in the bone marrow, accompanied by loss of normal B cells and leukemia cells that express CD19. Remission was ongoing 10 months after treatment. Hypogammaglobulinemia was an expected chronic toxic effect.

    T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia
    Michael Kalos1,2,*, Bruce L. Levine1,2,*, David L. Porter1,3, Sharyn Katz4, Stephan A. Grupp5,6, Adam Bagg1,2 and Carl H. June1,2,†
    Sci Transl Med 10 August 2011:
    Vol. 3, Issue 95, p. 95ra73
    DOI: 10.1126/scitranslmed.3002842
    http://stm.sciencemag.org/content/3/95/95ra73.short

    Tumor immunotherapy with T lymphocytes, which can recognize and destroy malignant cells, has been limited by the ability to isolate and expand T cells restricted to tumor-associated antigens. Chimeric antigen receptors (CARs) composed of antibody binding domains connected to domains that activate T cells could overcome tolerance by allowing T cells to respond to cell surface antigens; however, to date, lymphocytes engineered to express CARs have demonstrated minimal in vivo expansion and antitumor effects in clinical trials. We report that CAR T cells that target CD19 and contain a costimulatory domain from CD137 and the T cell receptor ζ chain have potent non–cross-resistant clinical activity after infusion in three of three patients treated with advanced chronic lymphocytic leukemia (CLL). The engineered T cells expanded >1000-fold in vivo, trafficked to bone marrow, and continued to express functional CARs at high levels for at least 6 months. Evidence for on-target toxicity included B cell aplasia as well as decreased numbers of plasma cells and hypogammaglobulinemia. On average, each infused CAR-expressing T cell was calculated to eradicate at least 1000 CLL cells. Furthermore, a CD19-specific immune response was demonstrated in the blood and bone marrow, accompanied by complete remission, in two of three patients. Moreover, a portion of these cells persisted as memory CAR+ T cells and retained anti-CD19 effector functionality, indicating the potential of this major histocompatibility complex–independent approach for the effective treatment of B cell malignancies.

    Like all news services NYT has exaggerated the story slightly. The man was not cured within weeks but entered a long remission, and this is a highly experimental treatment that only included three patients (of which only two showed strong benefits) which is nowhere near statistically enough when you consider the fact that sometimes cancers do go into spontaneous remission.

    Having said that it is very interesting work and hopefully we can see studies on this expanded in future.
     
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