thanks cj, chev,et.all. Cotara? What's happened since this 1998 update: TNT for Tumors By Sean Henahan, Access Excellence 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.
"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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