UCSD's Kipps Notes Early Success in Gene Therapy in CLL

[Guest guest]

[Personally, I'm very surprised this press release came out at this

time. There are 12 patients in this trial, and here comes a report on

the first six. 'Several' of those six produced CLL antibodies.

Generally speaking, reports come out months after a trial is

completed, the data tallied up, and the statistical software is done

torturing the data. I'm not sure why this has been released at this time.

This trial has long since been filled, and the first patient dosed in

I believe October 2007.

Interesting timing and results.]

Gene Therapy Protocol Activates Immune System In Patients With

Leukemia, Study Shows

ScienceDaily (Feb. 12, 2008) †" A research team at the s Cancer

Center at University of California, San Diego (UCSD) reports that

patients with chronic lymphocytic leukemia (CLL) who were treated with

a gene therapy protocol began making antibodies that reacted against

their own leukemia cells.

Researchers led by J. Kipps, M.D., Ph.D., inserted a gene with

the potential to activate an immune response -- a gene therapy

protocol developed at UCSD -- into six patients with CLL, the most

common form of adult leukemia. Several of the patients started making

antibodies that reacted against their own leukemia cells. When tested

in the lab, the antibodies also reacted with the leukemia cells of

other patients with the disease.

" The patient's own leukemia cells were modified outside of their body

and given back as a vaccine, " said Kipps. " The result raises hope that

it may be possible to activate a patient's immune system against their

own cancer. "

The patients were shown to make antibodies reactive with a

leukemia-associated antigen -- a protein made by leukemia cells that

can stimulate the body's immune system to produce antibodies -- called

ROR1. This antigen appears to be found only on the cell surface of the

leukemia cells, but not on normal cells, and serves as a receptor that

binds to a ligand called Wnt5a, which activates a pathway important

for the survival of the leukemia cells.

" The Wnt5a ligand interacts with ROR1 to enhance leukemia-cell

survival. Antibodies that react with ROR1 can interfere with this

survival signal and might also specifically target the leukemia cells

for destruction, " Kipps said.

He also noted that because the ROR1 antigen is found only on leukemia

cells, it could be developed as a very specific marker to monitor for

the continued presence of leukemia cells after treatment or for

identifying leukemia cells in patients with early disease, when the

cancer otherwise might not be detected. It also provides a much more

specific target for antibody therapy. Antibodies that target ROR1

would be unlike currently used antibodies, which bind antigens found

not only on leukemia cells, but also on normal cells. Because they can

destroy normal cells, the antibodies currently used to treat patients

with this leukemia can cause side-effects and weaken the immune system.

The ROR1 antigen is ordinarily found on a few cells in early embryonic

development and is not detected on adult human cells or tissues.

However, high amounts of this antigen are found on all the leukemia

cells of patients with CLL. In the PNAS paper, the UCSD researchers

present data on the leukemia cells of approximately 70 patients, all

of which expressed the ROR1 antigen.

The study will be published on line the week of February 11-15 in the

online edition of the Proceedings of the National Academy of Science.

Additional contributors at the s UCSD Cancer Center include first

author Tetsuya Fukuda, Liguang Chen, Tomoyuki Endo, Li Tang, Desheng

Lu, Januario E. Castro, Widhopf, Z. Rassenti, Mark

Cantwell, Cantwell and Prussak. The paper was

contributed by Dennis A. Carson, M.D., professor, s UCSD Cancer

Center and the Chronic Lymphocytic Leukemia Research Consortium at

UCSD. The work was supported in part by grants from the National

Institutes of Health, the Blood Cancer Research Fund of the s

UCSD Cancer Center and a grant from the Leukemia and Lymphoma Society

of America.

Adapted from materials provided by University of California - San

Diego, via EurekAlert!, a service of AAAS.