Cancer treatment enters trials

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Researchers at the School of Medicine are combining their artillery specialized for liquid and solid cancers to target the disease when it appears in the lungs

The latest research efforts, led by Dr. Lynn Wilson, a radiation oncologist specialist at the medical school and Yale-New Haven Hospital, combines the more traditional cancer treatment, chemotherapy, with transimmunization, a therapy that is usually used for cutaneous T-cell lymphoma — a form of lymphatic cancer that affects the skin. The study is entering Phase I clinical trials, the preliminary phase in which researchers use a small set of human subjects and examine the safety of the treatment.

The effects of transimmunization cause cancer cells to be converted, or differentiated, into dendritic cells — key players in the immune system also called antigen-presenting cells. These cells display the antigen on their surface in order to alert the immune system that a foreign body has attacked and tell other immune cells what invaders they are looking for in the body.

“This process has the purpose of boosting the immune system using photophoresis, which has been used for some time for the treatment of cutaneous T-cell lymphoma,” said Dr. Michael Girardi, professor of dermatology and sub-principal investigator of the project.

Photophoresis is a treatment in which white blood cells are passed through a thin plastic plate and then exposed to a UV light while in the presence of specific chemicals. This process differentiates the cells into dendritic cells, which then stimulate the immune system by presenting the antigen. Girardi said this stimulates the immune response to attack cancerous cells.

Wilson said his study is the first to apply this process to a solid tumor, the culprit of lung cancer.

The project was awarded funding by the State of Connecticut Department of Public Health approximately two weeks ago and will involve 16 subjects, all sufferring from end stage lung cancer.

“End stage lung cancer is something that currently has no known cure, and although the standard therapy is chemotherapy, it is not effective,” Wilson said.

Eight to nine out of 10 lung cancer patients have been afflicted by the cancer through some sort of contact with cigarette smoke, either directly or second-hand, he said. In this study, the vast majority of the subjects’ lung cancer is related to smoking.

Cigarette smoke’s direct correlation with lung cancer is the reason has catapulted it into the public health measures arena as of late, said Dr. Lynn Tanoue, director of the Yale Lung Cancer Center. Although lung cancer does not fall into the realm of public health one would usually think of, infectious diseases such as HIV, a worldwide epidemic of lung cancer related to smoking has developed, Tanoue said.

“In Europe and Asia we are seeing a skyrocketing rate of lung cancer because smoking and lung cancer are no longer a western phenomenon as we had thought of them before,” she said.

Lung cancer claims more American lives than the next three most prevalent forms of cancer — colon, breast and prostate — combined, Tanoue said.

The harmful effects of cigarette smoke were first recognized about 50 years ago, and then United States Surgeon General Luther Terry first released a report on smoking and health in 1964.

Although the amount of lung cancer-related deaths has plateaued in the United States at about 160,000 per year, it has risen since the 1940s and a significant portion of the population still smokes, Tanoue said.

“In America, 25 percent of the population still smokes even though the effects of the cigarettes are well understood,” she said. “Twenty percent of American college students smoke at an age where, if they become addicted as young adults, they are likely to continue forever.”

Wilson said he is excited about the potential benefits this new approach could have for patients in the future, since the prognosis of end stage lung cancer patients is so poor.

“If it is successful, in the future we will be in a position to make new treatments for these patients and to set a new modality,” he said.

Researchers at the School of Medicine are pioneering a treatment combining chemotherapy and transimmunization to fight lung cancer, which smoking has elevated to a public health concern.
Michael Blank
Researchers at the School of Medicine are pioneering a treatment combining chemotherapy and transimmunization to fight lung cancer, which smoking has elevated to a public health concern.

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