In efforts to educate the body to fight off cancer,
researchers have found that some immune cells are "smarter"
than others. Working with collections of human cells,
Hopkins Kimmel Cancer Center scientists tested
kill-rates of two kinds of T-cells "primed" to home in on
myeloma, a cancer of the bone marrow. Those that live in
the bone marrow outperformed their counterparts circulating
in the blood by more than 90 percent.
"It is very difficult to design cancer therapies that
get the body's immune system to recognize and kill cancer
cells that the system has ignored for a long time," said
Ivan Borrello, assistant professor of oncology and director
of the research, which is published in the March 1 issue of
Cancer Research. "Now we have evidence that
'educating' T-cells in the bone marrow may be the most
effective way to get an anti-tumor response."
In nature, T-cells are responsible for identifying
cells that are foreign to the body, including genetically
altered cancer cells, and marking them for destruction. In
the Johns Hopkins study of both kinds of T-cells, those
from the blood and bone marrow, scientists mixed the
T-cells with magnetic beads coated with tumor antibodies, a
sort of "artificial intelligence" that activated and
expanded the T-cells' cancer-killing mode.
The marrow T-cells identified not only mature myeloma
cells but the primitive cells responsible for the disease.
Activated bone marrow T-cells stopped the growth of 86
percent of myeloma stem cell colonies, compared to 47
percent for activated T-cells taken from circulating blood.
The researchers' next step is to determine whether the
cells' ability to limit cancer growth in culture dishes
ultimately may do the same in patients.
Kimmel Cancer Center researchers are planning studies
in a small number of myeloma patients to test the activated
marrow T-cells alone and in combination with a myeloma
"While T-cells from circulating blood traditionally
are used in immunotherapy strategies because they are easy
to obtain and grow, they often don't recognize the tumor,"
Borrello said. "In the case of myeloma, we believe the
marrow T-cells have certain surface markers that may help
them migrate back to the site of the tumor." Moreover, said
Kimberly Noonan, researcher and first author of the paper,
"the marrow itself contains some type of stimulant to
attract the cells."
To treat patients, the scientists will collect a small
amount of bone marrow and, with relative ease, will grow
and activate large numbers of T-cells from that source;
these would then be given intravenously back to the
patients. However, according to Borrello, the researchers
may find that an additional cancer vaccine may increase the
overall anti-tumor effect of the marrow T-cells.
They also believe that patients with other blood, bone
marrow and solid tumors such as breast cancer may benefit
from this type of immunotherapy. Evidence from other
research groups indicates that breast cancer patients have
T-cells in their bone marrow that are specific to their
Myeloma strikes close to 16,000 Americans annually and
Other participants of this research are William
Matsui, Paolo Serafini, Rebecca Carbley, Gladys Tan, Hyam
Levitsky and Katherine Whartenby, all from Johns Hopkins;
and Jahan Khalili and Mark Bonyhadi, from Xcyte