A Radical Cancer Therapy! Do Not Hold Your Breath

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Matthew Herper, Forbes, May 26, 2014
www.forbes.com/sites/matthewherp ... w-well-cure-cancer/

Quote:

“CEO Jimenez is "a marketer by trade who, until he came to Novartis in 2007, managed brands like Clorox and Peter Pan Peanut Butter before running the North America business for Heinz, the ketchup maker. But a seat on the board of AstraZeneca got him interested in selling products that saved people’s lives. He was brought in to run Novartis’ $4 billion consumer products division, home to Triaminic and Theraflu, but was rapidly promoted to run drug marketing and then, in a surprise to everyone, made the chief executive. Jimenez’s predecessor, Daniel Vasella [a Swiss who obtained MD in 1980 from the University of Bern in Switzerland], saw in him someone who could pilot Novartis through what was going to be a tough time.

“Will CARTs work for all cancers? Targeted drugs like Gleevec are more effective against blood cancers than solid tumors like lung or breast cancer (which literally build walls of tissue to protect themselves); the same thing may be true with CARTs.

Note:
(a) This is the cover story, whose cover shows Novartis CEO and says,

“NOVARTIS' JOSEPH JIMENEZ[:] ‘THE PAIN OF HAVING TO TURN PATIENTS AWAY IS SUCH THAT WE ARE GOING AS FAST AS WE CAN.’
WILL THIS MAN CURE CANCER/  WITH A RADICAL NEW TREATMENT[,] HE IS BETTING BILLIONS ON CONQUERING OUR DEADLY FOR[.]”

(b) T Cell Therapy for Acute Lymphoblastic Leukemia (CTL019, formerly CART19). Children’s Hospital of Philadelphia, undated
www.chop.edu/service/oncology/pe ... t-cell-therapy.html
(“At this time, The Children's Hospital of Philadelphia is the only hospital enrolling pediatric patients on this trial”)
(i) The Web page states, “These [genetically modified T] cells are genetically modified to express a protein which will recognize and bind to a target called CD19, which is found on cancerous B cells.”
(A) CD stands for “cluster of differentiation.” You do not need to know why such a strange name was given. Suffice it to say that each member (associated with a number) is a protein on the surface of a cell.
(B) CD19
www.ncbi.nlm.nih.gov/gene/930
(“a cell surface molecule which assembles with the antigen receptor of B lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation”)
(C) The quotation in (B) is conceptualized by Figure 3
www.springerimages.com/Images/RS ... -1-4419-7185-2_13-2
at van der Burg M et al, Dissection of B-Cell Development to Unravel Defects in Patients with a Primary Antibody Deficiency. Advances in Experimental Medicine and Biology, 697: 183-196 (2011)
in Hot Topics in Infection and Immunity in Children VII.
(ii) This Web page cited
Grupp SA et al, Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia. N Engl J Med 2013; 368:1509-1518.
www.nejm.org/doi/full/10.1056/NEJMoa1215134

(c) The (b)(i) is untrue. CD19 occurs on normal (non-malignant) B cells, too. The Forbes article points out, “The current CARTs kill not just cancer cells but any B-cell, the type of white blood cell that goes wrong in leukemia. Patients are likely to get injections of a protein that B-cells make, called gamma globulin, for the rest of their lives.”

(d)
(i) Paragraph 2 of the article remarks, “Nothing except a crazy experimental treatment never before given to a child: Blood was taken out of 6-year-old Emily’s body, passed through a machine to remove her white cells and put back in. Then scientists at the University of Pennsylvania used a modified HIV virus to genetically reprogram those white cells so that they would attack her cancer, and reinjected them.”
(ii) Further down the report comments, “With CARTs [chimeric antigen receptor T-cells] scientists add a man-made receptor–the chimeric antigen receptor–assembled from mouse antibodies and receptor fragments. A gene code for the man-made receptor is inserted into the T-cell’s DNA with a virus, usually a modified HIV. If the receptor sees cancer, not only does it kill it, it starts dividing, creating a cancer-killing army inside the body.”
(iii) Herein lies the rub. All gene therapies so far bring about cancers later, because the alien gene inserts randomly in host’s DNA.