San Diego, CA (5/6/98)- Researchers believe some tumors
not responsive to conventional chemotherapy might improve after a blast
of TNT. In this case, they are not talking about explosive charges, rather,
a new antibody based approach called tumor necrosis therapy.
Tumor
necrosis therapy utilizes monoclonal antibodies targeting intracellular
tumor antigens on necrotic (dead) tissue. This method overcomes some of
the limitations of current antibody-based therapeutic approaches, reported
Alan Epstein, MD, PhD, USC Medical Center, department of pathology, LA,
CA, at the 11th International Conference on Monoclonal Antibodies for Cancer.
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"Tumor necrosis therapy is a new concept in antibody cancer treatment.
One characteristic of cancer unique to all tumors is that they contain
large areas of necrotic lesions. Whereas most antibodies target extracellular
antigens, TNT employs antibodies targeting intracellular antigens exposed
on degenerating cells found in necrotic areas of tumors," said Epstein.
Over the past eight years, Epstein and colleagues have developed several
antibody candidates targeting DNA antigens in necrotic cells. Two of these
are being tested clinically. TNT1 is directed against DNA histone H1 complex
in the nucleosome, while TNT3 has the added advantage of targeting both
single and double strand DNA.
Current clinical trials link the antibody with the Iodine 131 isotope.
The idea is that the antibody binds to tumor and the radiation helps kill
it. Some 50 patients have been treated in the US, China, Mexico, Israel
and elsewhere.
The early studies indicate that the TNT approach should be applicable
to a wide range of cancers. No binding of the antibody in normal tissues
has been seen, and the antibody is not subject to antigenic modulation
or heterogeneity, typical problems with other antibody cancer treatments,
he said.
A clinical study conducted in China recently confirmed the safety of
this approach and was responsible for some dramatic remissions. In one
case, a wheel chair bound brain cancer patient who presented with no affect
or speech ability, was able after treatment, is now enjoying a normal life
and is doing extremely well, he reported.
"We really didn't expect TNT to be very useful in brain cancer. It was
through our collaboration with a Chinese hospital that saw 50,000 brain
cancer patients per year that we begin to see results in some patients,
when antibody was given immediately following surgery and then continued
monthly for four months," he said.
A safety study of 131I-chTNT-1/B is now underway at four centers in
the US for treatment of malignant glioma (brain cancer). The study will
enroll up to 24 patients with recurrent supratentorial anaplastic astrocytoma
and glioblastoma multiforme forms of brain cancer who are candidates for
surgical treatment. The patients will receive the antibody by continuous
infusion directly into the brain tumor.
It is likely that TNT therapy would prove most useful when used in combination
with standard chemotherapy or radiation therapy, he added.
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