Targeted immunotherapy advances treatment of cutaneous malignancies

Chicago - The use of targeted immunotherapy approaches is advancing for the treatment of numerous cutaneous malignancies including melanoma, cutaneous T-cell lymphoma (CTCL) and basal cell carcinoma (BCC), says Larisa Geskin, M.D., of the University of Pittsburgh.

Dr. Geskin presented "Immunotherapy of Cutaneous Malignancies" at the American Academy of Dermatology's Academy '05 here.

Immune responses

Over the past decade, researchers have come to understand that the immune system can be altered to initiate directed immune responses against infection and cancer.

"The skin is an immunological environment, and many processes in our body start on the skin but result in different immune responses depending on the immunological setting," Dr. Geskin says. "Depending on the environmental circumstances, we may either generate an immune response that results in effective immune response against infection and/or cancer or we can become tolerant to it. It is important to recognize that our immune system can be altered in a way that can create directed immune responses.

"To simplify, to create an immune response against tumor resulting in tumor rejection, we would try to induce cytotoxic T-cell responses with Th1-skewing of the helper population, but if we want an antibody response to bacteria, for example, we may need to create a Th2-skewing of the immune response," she says. "We can do this by using different vaccines, cytokines, etc. We can manipulate our immune system in a way that creates the necessary immune response."

Targeted therapies

"The immunotherapy field is just being developed, but a prototypical agent is imiquimod, which is a cream approved for the treatment of BCC and actinic keratosis," she says. "The way the cream works is by stimulating the patient's own immune system, production of interferon and TNF and other cytokines to reject the patient's own tumor, which is a great idea. Of course, imiquimod is far from being a perfect anticancer drug by any means, because of its relatively low cure rates and significant expense, but just the thought of a cream being an anticancer agent is interesting.

"The goal of development of anticancer therapies is to create a drug that would be specific for the targeted malignancy, would cause no harm to the surrounding tissues, and would have low overall side effect profile and high cure rates, and of course would be inexpensive. I like the thought of a cream being used in such a non-invasive way," Dr. Geskin tells Dermatology Times.

Imiquimod is a good initial step in targeted therapies, but will likely be replaced with more selective agents down the line, she says. The noninvasive method is very appealing for further development in superficial cancers such as BCC as well as other malignancies.

"The idea behind the use of targeted therapies in the treatment of cancer is to deliver a drug that is very selective to the tumor, so you don't get all those terrible side effects you get with chemotherapy but you target a specific thing - tumor only." This way, patients might have tumor regression with minimal side effects, she says.

Melanoma

Melanoma has been a target for immunotherapy development for many years. However, many researchers have fallen short in progressing from the bench to the clinically available treatments. One obstacle has been durable immune tolerance in most patients with late stage disease. Yet many agents, including interferon and interleukin-2, have demonstrated potential in treatment.

The current paradigm shift is a focus on earlier disease, when immune tolerance is not yet established and immunotherapies have a chance, Dr. Geskin says.