Thursday, June 5, 2014

Will This Man Cure Cancer?

While in the passenger seats of one of my housemates car, I picked up a Forbes magazine from the dashboard published in May 2014.  The large block lettering on the cover read "WILL THIS MAN CURE CANCER?" below a picture of a professional looking man in a full suit.  After spending ten weeks studying many different topics regarding cancer research,  I wondered what this business/financial news based magazine was to say about curing cancer.  The man on the cover is Joseph Jimenez, the CEO of Novartis, a Swiss pharmaceutical company.

  Jimenez plans to "double down" on cancer related drugs by spending the majority of Novartis' budget on cancer therapies.  According to Forbes, Jimenez is a man that should be listened to when it comes to making money.  He transformed Gleevec(tyrosine-kinase inhibitor) from a 400 million dollar annual profit to a 4.5 billion dollar annual profit.  The six page article begins by discussing the case of a five year old girl diagnosed with acute lymphoblastic leukemia(ALL).  Today 85% of ALL patients are cured with FDA approved chemotherapeutic treatment.  This particular young girl is part of the remaining 15% uncured patients.  Her cancer returned while she was waiting for a bone marrow transplant.  Oncologists decided to try a treatment in which they removed blood from the patient and passed it through a machine which removes white blood cells.  They used a modified HIV virus to genetically reprogram those white bloods cells so they would attack cancer cells.  I decided to further research this process of immunotherapy described without much detail in Forbes magazine.
The cornerstones of cancer treatment have developed from surgery, radiation and chemotherapy to targeted chemotherapeutic treatment and immunotherapy.  Of course a combination of these therapies are still used to treat patients through the developing stages of cancer.  The first approach to immunotherapy in early clinical trials has been Adoptive Cell Transfer(ACT).  T-Cells are first collected from the patient and then genetically engineered to produce special receptors on their surface called chimeric antigen receptors(CAR's).  CAR T-Cells are then infused back into the patients bloodstream to hopefully target and kill cancer cells that harbor the antigen on their surface.  CARs allow T-Cells to recognize specific proteins on the surface of mutated B-cells.  CAR T-Cells have only been used in clinical trials treating blood cancers so far.

A brief report published by the New England Journal of Medicine in April 2013 was one of the first to address the ability of CAR T-Cells to treat leukemia.  The purpose of this trial was for CAR T-Cells to target the antigens CD19 and CD20.  The two case reports in the article use the CART CTL019 to treat two children with refractory and relapsed ALL.  The first patient while experiencing her second reoccurrence of ALL and no longer responding to intensive chemotherapy, had her peripheral blood mononuclear cells(PBMC) collected.  The patients was then infused with CTL019 cells with anti-CD3 and anti-CD28 antibodies to express anti-CD19 CARs.  No related toxic effects were recorded.  Patient 2 was treated with the same process.  
Table 1:Induction of Molecular Remission in Blood and Bone Marrow.  
As noted in Table 1 from this case study, remission of leukemia was measured 1 month after infusion in both patients.  These results were confirmed by molecular detection of clonal IGH by a deep sequencing process.  The diagnosis of leukemia and other B-Cell malignancies can be frequently detected by clonal immunoglobin heavy chain gene arrangements.  These IGH's were detected in this experiment through polymerase chain reaction (PCR) amplification.  Seen in both patients, is a decrease in IGH total reads and unique reads.
Immunotherapy cancer treatment protocols like the ones presented in these two case studies absolutely need further research and confirmation before FDA approval.  Remissions were sustained in one patient while one patient experienced a relapse due to the emergence of CD-19 blasts.  On the brighter side, the induction of complete remission in refractory CD-19+ ALL after infusion CAR T-Cell is very encouraging and leading the way for similar experiments done in 2014 and the future.

Work Cited
 Gruppe, Stephan. "Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia — NEJM." New England Journal of Medicine. N.p., 18 Apr. 2013. Web. 06 June 2014. 

"CAR T-Cell Immunotherapy for ALL." National Cancer Institute. N.p., 6 Dec. 2013. Web. 06 June 2014. 

"Novartis Highlights Research on Investigational, Personalized T Cell Therapy CTL019 in Patients with Forms of Acute and Chronic Leukemia." Novartis, 17 Dec. 2013. Web. 06 June 2014.