'Ideal' Peptide Binds to Leukemia Cells - May Help Deliver Drugs

[Guest guest]

UC DAVIS RESEARCHERS REPORT NEW MOLECULE THAT TARGETS LEUKEMIA AND

LYMPHOMA

CELLS

Peptide shows promise as an imaging and therapeutic agent for lymphoid

cancers

(SACRAMENTO, Calif.) -- UC Cancer Center researchers have

developed a

novel peptide that binds to the surface of leukemia and lymphoma

cells with

extremely high affinity, specificity and stability, and demonstrates

remarkable promise as a tool to help image tumors and deliver anti-

cancer

drugs. The research is reported in the July issue of Nature Chemical

Biology.

" We believe that this peptide has great potential for becoming a new,

effective imaging and therapeutic agent for patients with lymphoid

cancers, " said Kit Lam, professor and chief of hematology and

oncology at UC Cancer Center and senior author of the paper.

The peptide – named LLP2A by Lam – binds to a receptor found on the

surface of lymphocytes. In the Nature Chemical Biology paper, Lam

reports that LLP2A is attracted specifically to malignant

lymphocytes, not healthy ones.

The next step will be to evaluate the binding of LLP2A in a larger

number

of human lymphoma biopsy samples. If those results are positive, Lam

plans

to test the peptide as a lymphoma imaging agent in patients.

Experiments

are already under way at the UC School of Veterinary Medicine to

evaluate LLP2A in dogs with naturally occurring non-Hodgkin's

lymphoma. In

addition, Lam and his colleagues have begun testing the peptide as a

drug-delivery vehicle for lymphoma tumors in mice.

LLP2A is intended to work like a monoclonal antibody – but a peptide

is

much smaller than an antibody and has the potential to infiltrate

cancer

cells more successfully. Monoclonal antibodies, engineered to lock

onto a

specific target molecule, are used to carry radioactive isotopes or

anti-cancer drugs directly to a tumor. Three monoclonal antibodies,

rituximab (Rituxan), ibritumomab tiuxetan (Zevalin), and tositumomab

(Bexxar), have already been approved by the Food and Drug

Administration

for the treatment of B-cell lymphoma. These antibodies have drawbacks,

however: They bind to healthy lymphocytes along with malignant ones;

in addition, they do not bind to T cells and therefore can't be used

to treat

T-cell lymphoma.

In contrast, LLP2A binds to both B-cell and T-cell lymphoid cancer

lines,

and has low affinity for normal T or B lymphocytes. It also has lower

uptake in the liver and spleen than the monoclonal antibodies now on

the

market for lymphoma treatment.

" We believe LLP2A may be an ideal vehicle for the delivery of

radionuclides, cytotoxic agents, toxins, cytokines and nanoparticles

to

lymphoid cancers which include non-Hodgkin's lymphoma and acute

lymphocytic

leukemia, " Lam said.

In their paper, Lam and his colleagues report that they have already

used

LLP2A to successfully image lymphoid tumors in living mice. The

researchers

coupled near-infrared fluorescent dyes to LLP2A peptides; when the

dye-tagged peptides found and locked onto a tumor, the tumor became

visible

to a near-infrared scanner.

LLP2A was identified using a combinatorial chemistry method Lam

developed

more than a decade ago. Known as the " one-bead-one-compound " method,

Lam's

technique allows scientists to synthesize millions of novel compounds

in

less than a week and analyze them in a few days.

UC Cancer Center is a National Cancer Institute-designated

cancer

center serving the Central Valley and inland Northern California, a

region

of more than 6 million people. Its research program is made up of 180

scientists on three campuses: the UC Medical Center campus in

Sacramento, the UC main campus in , Calif., and the

Lawrence

Livermore National Laboratory in Livermore, Calif.

- - - - - - - - - - - - - - - - - - - - - - - -