This is a new day! With smart T-Cell vaccines

Recently I had the incredible experience of having a face-to-face discussion with Dr. Lou DeGennaro, the Chief Mission Officer of the Leukemia & Lymphoma Society (LLS) in the United States, on the up-and-coming potential cure for those with 17p deleted CLL/SLL -- CARs (chimeric antigen receptors). My son Rocky made it all happen for me and I am so grateful.

On behalf of the Arizona Chapter of the LLS, Dr. DeGennaro was scheduled to give a presentation at the Ritz-Carlton in Phoenix on the topic “Someday is Today: A discussion on the latest advancements and strategies in cancer research.” Rocky invited me to the event and took me to a cocktail reception before the presentation. So with my glass of red wine in hand, Jim Brewer, the Executive Director of the Phoenix LLS, introduced me to “Dr. Lou”.

We were having such an animated and scientific discussion about CARs that I think we were boring some of the people in our circle. LOL. I have discussed CARs in prior posts, but it doesn’t hurt to summarize what this means to my potential cure.

LLS is funding Carl H. June, M.D. at the University of Pennsylvania in Philadelphia for the personalized cancer therapy he initiated on T-cell re-engineering. Dr. Weirda at M.D. Anderson is also researching CARs. In fact, there are about seven CARs trials taking place today at a variety of locations. Here is the summary of the first procedure at UPenn:

(1) T-cells are removed from the patient’s body through a procedure called “apheresis.” Blood is removed from the patient and cells are separated through a process of centrifugal force. (NOTE: I had this done when I donated my cells to science. My cells were injected in a number of mice in the NIH lab to research why I am so resilient. LOL.) This is a painless procedure, similar to donating blood to a bank. My friend Janis witnessed me resting in the bed during this procedure in June of last year.

(2) The extracted T-cells from the patient are engineered to express a “chimeric antigen receptor” (CARs). The T-cells are harvested and injected with benign HIV cells.

(3) After the T-cells are re-engineered, they are ready to be infused back into the patient.

(4) The T-cell “serial killers” erradicate the cells with the CD19 enzyme, and the procedure climaxes at about two weeks or so. Because healthy B-cells also have CD19, the engineered T-cells cannot differentiate and kill them as well.

(5) The patient often has the worst case of the “flu” ever with sometimes a fever of 104 degrees.

NOTE: The first three clinical trial subjects at UPenn were rushed to the hospital thinking they were dying. Shortly after the episode, the three patients were tested for cancer, and found that there was no leukemia in two and a minimal residual disease (a small number of leukemia cells remaining, but no symptoms or signs of disease) in one.

NOTE: I was unable to credit the graphic designer who did this informational graphic, because there was no name attached to the image. If you are out there, let me know and I will give you full credit for your work.

For those of you not wanting the timeline details, skip to the paragraph after the indented text.

CARs TIMELINE

• In 1987 it was discovered that CD28 is the gatekeeper for T-cell proliferation.

• CARs research was actually pioneered in vitro in 1989, but it took two decades for it to be tried on humans.

• In 1993 a CD culture system was produced with CD3/CD28 beads. Cell size were 4.5 microns each and they were grown in vitro (test tubes)

• Three clinical trials were conducted in 1998 with HIV patients.

The first HIV CAR patients were treated targeting CD4z modified T-cells. They were infused with the re-engineered T-cells like a blood transfusion. 41 of 43 patients have CAR T-cells that have persisted more than a decade with no adverse effects.

• In 2006 the first cancer patients were treated NCI and in the Netherlands. No clinical efficacy, because T-cells did not engraft on the patients. Cells had half-lives and lasted less than a week.

• Clinical trial.gov #NCT01029366 at the University of Pennsylvania treated 12 subjects as of September 2012:

July 31, 2010 the first cancer subject was treated. The target was CD19, since it is expressed on the surface of most B-cell malignancies. Ten patients had CLL/SLL and two had ALL (acute lymphocytic leukemia). The patients were infused a 10-30-60% dose for three days. Seven had a complete remission (CR). Two had a partial remission (PR), and three had no remission (NR). No one has relapsed, and T-cells continue to produce antibodies (Now for two years). Each person had a total of 3.5 to 7 pounds of tumor cells removed from their body through this procedure. Each re-engineered CAR T-cell (“serial killers”) can kill 1,000 tumor cells.

My Australian blog friend John also passed on these links for my nerdy friends wanting more information on CARs:

• Interview with William Wierda on CARS at

http://www.patientpower.info/video/new-t-cell-car-research-for-cll?autoplay=1


• CLL Global Research magazine 2-2012, particularly Page 4 for Kinase inhibitors & CARS at http://www.cllglobal.org/Resource_Files/CLL_NL_Issue2_2012.pdf 


• CARS research, a talk by Dr. carl June at

http://www.youtube.com/watch?v=jQfFCC6i5_o.

The initial problems with the CARs trial at UPenn were:

(1) the enzyme CD19 is also found on normal B-cells, so patients are left immune compromised,

(2) Because the T-cells are harvested from each patient, it is an expensive and time-consuming procedure, and

(3) the patient has to be in good enough health to provide enough T-cells.

Researchers are getting closer to a cure. Future solutions:

(1) Now the new procedure involves re-engineering T-cells to bind with a certain protein – ROR1, which is expressed in leukemia cells. ROR1 becomes the target.

(2) In order to be more cost-effective, as well as efficient, researchers are exploring using healthy donor cells. This will also help those patients who are deficient in T-cells to harvest.

An interesting bit of information is that research and finding treatments and cures for blood cancers often leads to application to other cancers. For example, the CARs trial at the University of Pennsyvania is now using the concept of the re-engineered T-cells for trials in pancreatic cancer. This CARs immunotherapy is a cure for leukemia and it is just around the corner. This is a new day!

Check out this video:

http://vimeo.com/54668275