"Killer" Cell Line Shown to Cure Leukemia in Mice

preis at wista.wistar.upenn.edu preis at wista.wistar.upenn.edu
Wed Aug 31 14:01:32 EST 1994


                        
                     For Immediate Release
   
   "KILLER" CELL LINE SHOWN TO CURE LEUKEMIA IN MICE
   
   Philadelphia, PA, August 31, 1994....Scientists at The Wistar Institute
have demonstrated that a "killer" cell line developed at the Institute
holds promise for the treatment of a great variety of cancers, both of the
blood and solid tumors.
   This line, known as TALL-104, has been shown to reverse and eradicate
human acute myelogenous leukemia, an aggressive form of blood cancer, in
SCID mice--mice whose immune system is genetically deficient and who are
thus unable to fight disease on their own.  The cell line used was derived
from a child with a rare form of T-cell leukemia by Daniela Santoli,
Ph.D., a professor at Wistar and senior author of a paper published in the
September issue of the Journal of Clinical Investigation, a publication of
The Rockefeller University Press.
   In the experiments described by Santoli and co-authors Alessandra
Cesano, Sophie Visonneau, Livia Cioi, and Giovanni Rovera, all of Wistar,
and Steven C. Clark of Genetics Institute, Inc. in Cambridge,
Massachusetts, the leukemic mice were injected with TALL-104 cells in
conjunction with recombinant IL-2 or IL-12, hormones able to support the
tumoricidal function of T-cells.  (IL-12, or Natural Killer Stimulatory
Factor, was identified  by another Wistar Institute scientist, Giorgio
Trinchieri, and subsequently was purified and cloned by Dr. Trinchieri in
collaboration with Genetics Institute, Inc.)  To prevent proliferation of
the TALL-104 "killer" cells in the mouse tissues and to allow them to die
off after they had done their work of destroying the cancer cells, the
"killer" cells were irradiated prior to being injected into the animals. 
   If this new method can be used in humans, it might be considered an
improvement of the adoptive transfer therapy approach developed by  
               
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Dr. Steven A. Rosenberg of the National Institutes of Health, in which
blood cells from cancer patients are grown and stimulated with IL-2 in a
test tube to generate lymphokine-activated killer cells, known as LAK, and
introduced back into the same patient's body with IL-2. 
   TALL-104 cells are more potent in the test systems tried to date than
LAK cells and are able to recognize and kill a far greater spectrum of
tumors than LAK cells.  Because they are such potent killers, they require
less IL-2 which can be toxic if used in the amount necessary for
conventional LAK therapy.  TALL-104 cells eventually might be used in
every cancer patient undergoing an immunosuppressive regimen, regardless
of genetic makeup, whereas LAK cells are derived from the patient being
treated.  TALL-104 cells are also "immortal," meaning that they can be
grown in unlimited supplies, whenever needed, and can be introduced into
the body in repeated injections, thus increasing the therapeutic
efficacy.  LAK cells, on the other hand, die off after a few weeks in the
test tube and, therefore, provide a limited supply of material for
therapy. 
   In the experiments described by Santoli and colleagues, a single
injection of TALL-104 cells into the leukemic mice significantly prolonged
their life span; complete eradication of the transplanted leukemia in the
mice occurred when TALL-104 cells were injected three times at close
intervals.  Data from preliminary experiments show that the TALL-104
"killer" cell line functions effectively also in normal
(non-immunodeficient) leukemia-bearing mice.
   For reasons not yet understood, in the animal models TALL-104 cells
seem to recognize and kill selectively all malignant cells, either solid
tumors or in the blood, without toxic effects on normal tissues.  This
means that they have potential application for a variety of malignancies,
including leukemias, lymphomas, and breast, brain and prostate cancer.  
Dr. Santoli feels that the cell line will prove most effective as a
clean-up mechanism, purging residual cells after the patient has been
treated with conventional means such as chemo- or radio-therapy; its use
in this fashion could prevent relapse of the disease, which often proves
fatal.  TALL-104 therapy also appears to be more promising than LAK
therapy in cases of advanced cancer, due to the high potency of this
"killer" clone.

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   Dr. Santoli's laboratory is studying further the use of TALL-104 cells to 
improve techniques of bone marrow purging.  Her recent data show that
irradiated TALL-104 cells can completely and safely eliminate cancer cells
from bone marrow.  This purging technique may be applicable to any cancer
involving the bone marrow, such as leukemia, neuroblastoma and breast
cancer.   Using the TALL-104 cells in this fashion as a purging agent in
bone marrow transplantation, followed by the adoptive transfer therapy
described above, is likely to lead to a total eradication of malignant
cells in the patient's body. 
   This research is being supported by grants from the National Institutes
of Health, American Cancer Society, and Josi Carreras International
Leukemia Foundation.
   The Wistar Institute is the oldest independent biomedical research
institution in the United States, having been founded in 1892.  Its
scientists specialize in the study, at the cellular and molecular level,
of malignant, degenerative and infectious diseases.  The Institute is one
of fourteen centers nationally that have been designated Basic Cancer
Research Centers by the National Cancer Institute.
               
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The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104

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Diana Burgwyn, Public Affairs Manager
Phone: 215-898-3716



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