Fused cells hold promise of cancer vaccines

Rcjohnsen rcjohnsen at aol.com
Wed Mar 22 14:39:31 EST 2000


Fused cells hold promise of cancer vaccines

By J. Travis

   What a shocking development. With small pulses of electricity, scientists
have merged human-tumor and immune cells to create personalized vaccines
against a deadly cancer.
   In the first trial of this strategy in people, 7 of 17 patients with kidney
cancer that had spread to other tissues developed tumor-specific immune
responses after several vaccinations with the fused cells. Indeed, while
conventional therapy keeps alive fewer than 10 percent of patients with
advanced kidney-cancer, four people in the vaccine trial experienced a complete
remission, Alexander Kugler of the University of Göttingen and his German
colleagues report in the March Nature Medicine.
"This is very impressive," says Donald W. Kufe of the Dana-Farber Cancer
Institute in Boston, who first showed that such hybrid-cell vaccines could
trigger an immune attack on cancers in animals.
   While researchers must do further work with more patients to confirm the
vaccine strategy, the results bring renewed attention to specialized immune
sentinels called dendritic cells. These cells patrol the human body, normally
displaying bits of invading viruses or bacteria and ordering other immune cells
to seek and destroy microbes bearing those fragments.
   In the early 1990s, scientists seeking to unleash the immune system on
cancer cells learned to grow human dendritic cells in the laboratory. That led
to the first dendritic cell vaccines, created by exposing the immune cells to a
tumor antigen, a protein on the surface of cancer cells. 
   In initial trials, people with lymphoma, melanoma, or prostate cancer who
received dendritic cells primed with a known tumor antigen showed strong
anticancer immune responses (SN: 1/13/96, p. 23; 6/13/98, p. 380).
   Hoping to create individualized vaccines without requiring that the tumor
have a known antigen, Kufe's team in 1997 fused whole cancer cells with
dendritic cells. They theorized that the dendritic cells would then alert the
body to multiple tumor antigens, including those that researchers had not yet
isolated.
   "One of the advantages of this approach is that they're delivering not a
particular antigen . . . but the whole antigenic content of a tumor cell," says
Eli Gilboa of the Duke University Medical Center in Durham, N.C.
After Kufe's animal testing proved promising, Kugler's group rushed to try
similar vaccines in kidney cancer, which has no recognized tumor antigen. The
investigators fused tumor cells from each patient with dendritic cells from
another person, a hybrid they hoped would arouse the immune system even more
than one made from the patient's own dendritic cells.
    Before injecting the hybrid cells into people, the scientists irradiate the
cells so that they can't grow out of control and create a new cancer threat.
The biggest concern investigators have about the vaccine strategy, says Kufe,
is that it may also trigger a person's immune system to attack healthy tissues.
After all, a cancer cell is largely a normal cell.
   Yet neither the animals receiving the hybrid cancer vaccines nor the people
in the German trial revealed such autoimmune side effects. "Autoimmunity is
clearly a possibility, but it hasn't been seen. No one knows why, but that's
the good news," says Kufe, who has begun testing a hybrid vaccine on breast
cancer.
   A research group in Berlin is working with a melanoma hybrid vaccine, and
about 40 percent of patients in that trial are responding, notes Kugler. His
group plans to directly compare the kidney cancer vaccine, which had a similar
immune response rate, with the current treatment standard of chemotherapy and
immune-stimulating chemicals such as interferon.
   Kufe predicts that scientists will find ways to make a larger percentage of
cancer patients respond to the vaccines. "There are a number of strategies to
make this [approach] even more potent," he says.

>From Science News, Vol. 157, No. 10, March 4, 2000, p. 149.

Fused cells hold promise of cancer vaccines

A vaccine composed of tumor cells fused to immune cells has helped several
people survive advanced kidney cancer.
References:

Kufe, D.W. 2000. Smallpox, polio and now a cancer vaccine? Nature Medicine
6(March):252.
Kugler, A., et al. 2000. Regression of human metastatic renal cell carcinoma
after vaccination with tumor cell-dendritic cell hybrids. Nature Medicine
6(March):332.
Further Readings:

Fackelmann, K.A. 1998. Immune attack on cancer. Science News 153(June 13):380.
Gong, J. . . . D. Kufe. 1997. Induction of antitumor activity by immunization
with fusions of dendritic and carcinoma cells. Nature Medicine 3(May):558.
Hart, I., and C. Colace. 1997. Fusion induces tumour rejection. Nature 288(Aug.
14):626.
Travis, J. 1996. Immune cells primed for cancer vaccine. Science News 149(Jan.
13):23.
Sources:
Eli Giboa
Duke University Medical Center
Science Research Building
Durham, NC 27710

Donald W. Kufe
Dana-Farber Cancer Institute
Harvard Medical School
Division of Cancer Pharmacology
44 Binney Street
Boston, MA 02115

Alexander Kugler
Department of Urology
University of Göttingen
Germany





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