HIV the gift that keeps on giving.

While Dr. J. was on vacation, the dinner conversation turned to a new breakthrough in the cancer field. Dr. J.’s astute mother in law picked up the story on the news, and blindsided Dr. J. and Mrs. Dr. J. (who is more up on cancer news than Dr. J.). Dr. J. intended to look it up when he returned from vacation, but tripped over this synopsis at the nerd-humor site xkcd.com.

Basically, Chronic Lymphogenous Leukemia (CLL) is a slow growing cancer of either the B or T lymphocytes. It can be managed with chemotherapy and medication for many years. Ultimately, the medications fail and the cancer becomes more aggressive, often entering an acute phase, and ultimately leading to the death of the patient. If you are going to get leukemia as an adult, CLL is is probably the one you would prefer to get.

The patient was diagnosed with CLL in 1996 and followed for 6 years.

In 2002 required treatment with rituximab (basically an anti-B cell antibody) and fludarabine (a purine analog that interferes with DNA synthesis and thus cell replication).

In 2006, he had progression his CLL and received more rituximab and fludarabine.

He did great until 2/2009 when the disease accelerated and infiltrated his bone marrow. This is when patients tend to go down hill from this disease. They busted out the big guns (more rituximab and the dreaded bendamustine) with only transient improvement.

So, in 12/09, they harvested his T-Cells and gave him a different anti-lymphocyte antibody (alemtuzumab) with some improvement.

This is where it gets interesting and cool. They made a lentiviral vector (basically a modified version of the Human Immunodeficiency Virus) that contained gene that was a chimeric protein. Now recall the gene for the chimeric protein was in the lentiviral vector. This vector (being derived from HIV and all) LIKES T-Cells. They then took his frozen T-Cells and, in vitro, transfected them with the virus, resulting in the gene for the chimeric protein being taken into the T-Cells.

The chimeric protein had a head that would bind to CD19 (a protein expressed on the leukemia cells), and a tail with CD3-zeta and CD137(aka 4-1BB) signaling domains. The chimeric protein would turn these modified T-Cells into ‘leukemia killers.

They gave the patient some more chemo to make room for the special T-Cells in his blood, then they gave him the modified T-Cells (called CART19 cells in the article) The cells expanded in his blood stream, and went after and destroyed his leukemia cells. The response was so robust that it made him acutely ill with ‘tumor lysis syndrome’ from which he recovered. He has had persistent low lymphocyte counts since the transplant, but has also remained disease free (10 months follow up at the time of writing the manuscript).

So, while this a a single case report, it is very promising as what it shows is that we can harvest immune cells from the body, and modify them to recognize cancer cells (in this case leukemia cells), and with some degree of specificity, kill them.

What’s more remarkable is that a VERY modified HIV virus is the vector used to transfer the chimeric gene to the patient’s T-Cells, and no the patient does not have HIV as a consequence.

The method used can probably be modified to go after a host of different tumors with time. It could also be modified, using a different viral vector, to perhaps transfer the correct version of beta-hemoglobin to red blood cell precursors in patients with sickle cell disease.

Clearly, however, more testing needs to be done before this technique is ready for prime time. One patient does not a miracle cure make, and in this case, this radical method to treat CLL was only done after standard therapies failed after 13 years of disease management.

Dr. J. thought, however, that it’s pretty remarkable, and worthy of sharing with his august audience.

Dr. J.