Transimmunization - Yale

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HAS YALE CURED LUNG CANCER?

Researchers seeking approval to test revolutionary process

Abram Katz, Register Science Editor 09/27/2003

Yale cancer researchers have translated enough of the immune system’s "Rosetta stone" to develop a new treatment that may decimate lung cancer.

Yale physicians are planning to study the patented and potentially revolutionary process in 20 lung cancer patients. If approved by Yale’s human investigation ethics committee, the study could commence within two months.

If the experiment succeeds — and there’s strong evidence to suggest it will — oncologists will have a powerful new weapon to kill tumors.

Dr. Richard L. Edelson directs the Yale Cancer Center, a national nexus of research into reinforcing the body’s natural defenses to do battle with malignancy. Edelson, who developed the treatment for cutaneous T-cell lymphoma, sees cancer as more than a scourge that kills half a million Americans a year. Cancer is an idiom that can tell how it damages the body — and give away its own vulnerabilities. "The best way to be a cutting edge cancer doctor is to learn the language that the cells speak," Edelson said. Physicians have medical jargon to define cases, he said. "The danger is that we begin to believe in the language created by man, not what the cells are speaking," Edelson said.

Edelson likes to compare cancer research to deciphering the Rosetta stone, a fragment of ancient rock bearing passages of hieroglyphics, Greek and another language. Efforts to translate hieroglyphics were futile until a British physiologist made a key observation that others had overlooked, Edelson said. "You must look at the correct details. Life is full of ‘ah-has!’ Life belongs to people who can see ‘ah-has!’" he said.

Edelson’s moment of insight came when he pondered the rash that proceeds (sic) cutaneous T-cell lymphoma. "If you have a disease feature there must be a reason for it. It tells you about the malignant cells," he said. Edelson and colleagues determined that the rash was caused by abnormal T cells locking onto another type of white cell, called a dendrytic cell.

Dendrytic cells absorb irregular cells, cut up their proteins and transport about 200,000 fragments to the cell’s surface. Normal T cells scrutinize the display, recognizing proteins that do not belong. Usually these are bacteria, viruses or other microbes. The T cells then set out to destroy them. In the case of T cell lymphoma, Edelson’s challenge was to stimulate normal T cells to kill irregular ones.

Edelson and colleagues developed a process now called photopheresis. White cells in the patient’s blood were separated, exposed to a photosensitive toxic chemical called psoralen, beamed with ultraviolet light, and re-infused. Results were surprisingly good. Since then, photopheresis has been performed more than 250,000 times at about 150 university medical centers around the globe.

But why was photopheresis so successful? During the therapy the patient’s white cells are separated and sent through 1-millimeter-wide tubes to ensure that the psoralen was illuminated. Unbeknownst to Edelson or others, monocytes, which can turn into dendrytic cells, were pressed against the tube walls and pulled off repeatedly. This stimulated conversion to dendrytic cells. The resulting dendrytic cells absorbed the cancerous T cells damaged by psoralen, and put the "targeting" fragments on display before the cells were returned to the patient. The dendrytic cells acted as an effective personal anti-cancer vaccine.

"Could we use this to treat all cancers with personalized cancer vaccines? It would be immunological jujitsu," Edelson said.

Edelson and partners took the lessons of photopheresis and created a new treatment called transimmunization. The initial target is lung cancer, because it is deadly and currently has no good treatment. Also, Edelson successfully used the technique to cure his father-in-law, but anecdotal evidence is not enough. So the Yale Cancer Center is planning to experiment on 20 lung cancer sufferers, if it receives permission from Yale’s Human Investigations Committee.

Dr. Michael Girardi, a dermatologist and member of Edelson’s team, said transimmunization differs in several ways from photopheresis. Tumors will be damaged with radiation or chemotherapy. Then tumor cells will be extracted and exposed to psoralen and UV. Instead of re-infusing the cells immediately, the dendrytic cells and dying cancer cells will be incubated overnight. Dendrytic cells will engulf and disintegrate the cancer cells. This will increase the percentage of dendrytic cells carrying cancer proteins, and able to spur the immune system, Girardi said. Dendrytic cells naturally seek out areas of damage in the body, so they hone in on the damaged cancer cells.

Anti-cancer vaccines are not a new idea. One problem may be that not enough antigens get into dendrytic cells. No single vaccine, or drug, or any other treatment is likely to be a "magic bullet" against cancer, Girardi said. "Anti-cancer therapy exerts a force on the tumor. But the tumor reacts, it is dynamic," he said.

Chemotherapy and radiation may weed out vulnerable cancer cells, leaving the resistant. An advantage of transimmunization is that treatments could be repeated and would not lose potency, Girardi said.

Edelson said, "When you’ve broken the code of the disease, you can prevent it from happening. "Now we understand the initial signal of cancer — it’s a normal language that becomes malignant."

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Abram Katz can be reached at 789-5719 or akatz@nhregister.com.

©New Haven Register 2003

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[teresag]

Interesting. At a previous job, I worked with photodynamic therapy (PDT), treating cutaneous metastases of breast cancer. Patients who had stopped responding to chemotherapy began responding again after photdynamic therapy, which is similar to the psoralen treatment described in the article. Our theory was that somehow the illumination of the cancer cells presents the cancer antigens anew to the immune system and the result is a renewed response to chemotherapy. We had 2 women with Stage IV breast ca who greatly outlived their expected lifespan. It's exciting stuff. I hope the Yale clinical trial is approved.