s Hopkins Press Release - CML Vaccine

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Public release date: 6-Jan-2010

s Hopkins researchers say vaccine appears to 'mop up' leukemia cells Gleevec

leaves behind

Team cautions that results are very preliminary and they cannot yet rule out

other reasons for success

s Hopkins Kimmel Cancer Center researchers say preliminary studies show that

a vaccine made with leukemia cells may be able to reduce or eliminate the last

remaining cancer cells in some chronic myeloid leukemia (CML) patients taking

the drug Imatinib mesylate (Gleevec).

Gleevec, one of the first targeted cancer therapies with wide success in CML

patients, destroys most leukemic cells in the body, but in most patients, some

cancerous cells remain and are measurable with sensitive molecular tests. These

remaining cells are a source of relapse, according to the investigators,

especially if Gleevec therapy is stopped.

In a pilot study published in Clinical Cancer Research, the s Hopkins

investigators used a vaccine made from CML cells irradiated to halt their

cancerous potential and genetically altered to produce an immune system

stimulator called GM-CSF. The treated cells also carry molecules, called

antigens, specific to CML cells, which prime the immune system to recognize and

kill circulating CML cells.

The study vaccine was given to 19 CML patients with measurable cancer cells,

despite taking Gleevec for at least one year. A series of 10 skin injections

were given every three weeks for a total of four times. After a median of 72

months of follow-up, the number of remaining cancer cells declined in 13

patients, 12 of whom reached their lowest levels of residual cancer cells. In

seven patients, CML became completely undetectable. Because the study was

conducted in a limited number of patients and not compared with other therapies,

the researchers warn they cannot be sure that the responses were a result of the

vaccine.

" We want to get rid of every last cancer cell in the body, and using cancer

vaccines may be a good way to mop up residual disease, " says Hyam Levitsky,

M.D., professor of oncology, medicine and urology at the s Hopkins Kimmel

Cancer Center. More research to confirm and expand the results is needed,

Levitsky said.

The investigators will be testing blood samples taken from the study patients to

identify the precise antigens that the immune system is recognizing. With this

information, they will tailor their vaccine for additional studies that monitor

immune response more precisely.

Patients receiving the trial vaccine experienced relatively few side effects

that included injection site pain and swelling, occasional muscle aches and mild

fevers.

According to the investigators, most patients with CML will need to remain on

Gleevec therapy for the rest of their lives. More than 90 percent of them will

achieve remission, but about 10 to 15 percent of patients cannot tolerate the

drug long term. " Often patients have low blood cell counts, fluid retention,

significant nausea and other gastrointestinal problems, " says B. ,

M.D., associate professor of oncology at the s Hopkins Kimmel Cancer Center.

Secondary therapies, including dasatinib and nilotinib, also have many side

effects.

Another common side effect of Gleevec, says , is fatigue. " Patients often

tell me that they feel about 80 to 90 percent of what they should, and over

time, this may have a big impact on their quality of life, " he says.

Gleevec also cannot be taken during pregnancy, and since one-third of CML

patients are in their 20s and 30s, many patients hoping to start families would

like to discontinue taking it.

" Ultimately, should this vaccine approach prove to be successful, the ability to

get patients off lifelong Gleevec therapy would be a significant advance, " says

Levitsky.

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The research was funded by the National Institutes of Health.

Study contributors include Yvette Kasamon, Jeanne Kowalski, Gocke,

Kathleen , Hua-Ling Tsai, Lu Qin, Chia, Barbara Biedrzycki, and

from s Hopkins; Carole from St. Agnes Hospital;

Garrett-Mayer from the Medical University of South Carolina; and

Harding and Guang Haun Tu from Cell Genesys, Inc.

Under a licensing agreement between BioSante Pharmaceuticals Inc. and the s

Hopkins University, Dr. Levitsky is entitled to a share of milestone payments

and a share of royalty received by the University on sales of GVAX. Dr. Levitsky

previously served as a paid consultant to Cell Genesys, which has since been

acquired by BioSante Pharmaceuticals Inc. The terms of this arrangement are

being managed by the s Hopkins University in accordance with its

conflict-of-interest policies.

On the Web: www.hopkinskimmelcancercenter.org