Weill Cornell/Ludwig Institute For Cancer Research Collaboration Identifies Two Antigens As Targets For Multiple Myeloma Vaccine

Now, joint research -- conducted by researchers at Weill Medical College of Cornell University and at the Ludwig Institute for Cancer Research (LICR) Memorial Sloan-Kettering Cancer Center Branch in New York -- has pinpointed two proteins that seem ideal targets for a vaccine against multiple myeloma, the second most common, and currently incurable, blood cancer.

The findings have just been published in the online edition of Blood and will appear in an upcoming print edition of the journal.

"This is all about understanding how the immune system works, and harnessing that activity to kill myeloma cells in a targeted way -- while leaving healthy tissues unharmed," explained senior researcher Dr. Hearn Jay Cho, Assistant Professor of Medicine in the Division of Hematology/Oncology at Weill Cornell Medical College in New York City.

After identifying the two cell proteins, called CT7 and MAGE-A3/6, in human myeloma cells, the Weill Cornell-LICR team now hopes to confirm that patients' immune T-cells can seek out and destroy them.

The next step -- probably not for a year or so -- would be to move a vaccine to clinical trials.

Multiple myeloma is a cancer of malignant bone marrow plasma cells and is diagnosed in 15,000 Americans annually.

"It's mostly a disease of the elderly," explained co-lead researchers Dr. Achim A. Jungbluth, of the LICR, and Dr. Scott Ely, of Weill Cornell Medical College. "As the elderly population increases, it's becoming more widespread. There's treatment available to temporarily halt the disease, but there's no cure, and most people with multiple myeloma die from their disease."

That's because initial treatments kill off most cancer cells but miss a tiny fraction that researchers now believe are largely responsible for relapse.

These cells evade chemotherapy and emerge later on, dividing uncontrollably as they cause a fatal relapse of disease.

But what if the immune system could be primed to recognize these rogue cells and destroy them before they trigger relapse?

The two newly identified antigens -- immune system "tags" -- may allow a vaccine to do just that.

In studies using bone marrow cells from multiple myeloma patients, the Weill Cornell-LICR team found that a very large fraction, over 80 percent, of multiple myeloma cells expressed CT7, and over 70 percent expressed MAGE-A3/6.

In fact, expression of CT7 increased with more advanced stage multiple myeloma. Higher levels of either protein were associated with higher rates of tumor cell growth. This close association with disease progression and proliferation suggests these antigens may also help spur malignancy and relapse, although more research is needed to confirm that role.

In the meantime, their potential as vaccine targets remains promising.

"Our findings support the idea that these antigens are strong immune markers for proliferating cells," said Dr. Cho, who is also Assistant Attending Physician at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

The success of any potential cancer treatment must be weighed against its potential for harmful side effects, of course. But Drs. Jungbluth and Ely said CT7 and MAGE-A3/6 are uniquely positioned to get around that problem.

"It appears these antigens are really only expressed in two tissue types -- proliferating cancer cells, and what we call 'germ' cells, which include the sperm and egg, and cells in the placenta," he explained.

Luckily, nature has provided the immune system with a built-in "ignore" function when it comes to these reproductive cell types.

"That means any vaccine targeting CT7 or MAGE-A3/6 probably won't harm normal, healthy tissue in most patients," Drs. Jungbluth and Ely said.

The next step, the researchers said, is to see if T-cells from multiple myeloma patients can recognize and attack cells bearing the antigens. Those laboratory studies are currently underway.

If that research proves fruitful, clinical trials could come a year or two later, according to Dr. Cho.

"In general, this whole strategy of harnessing the immune system to fight cancer is still being worked out," he said. "But its potential could be enormous. It's bringing fresh hope, not just to patients with multiple myeloma, but to everyone struggling with cancer."

The study was funded by a Specialized Center of Research (SCOR) grant from the Leukemia and Lymphoma Society (Principal Investigator Dr. Selina Chen-Kiang at Weill Cornell), the Cancer Research Institute, and the Dorothy Rodbell Cohen Foundation for Sarcoma Research.

Senior author Dr. Cho was supported by a Postdoctoral Fellowship for Physicians from the Howard Hughes Medical Institute and by the Hermione Foundation.

Co-researchers included Dr. Maurizio DiLiberto, Dr. Ruben Niesvizky, Dr. Yao-Tseng Chen, and Dr. Selina Chen-Kiang -- all of Weill Cornell Medical College; Barbara Williamson, Denise Frosina, and Dr. Lloyd J. Old -- all investigators of the Ludwig Institute for Cancer Research Memorial Sloan-Kettering Cancer Center Branch; and Dr. Nina Bhardwaj -- of New York University School of Medicine.