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Adoptive Cell Transfer: A Promising New Melanoma Treatment

Doctors Are Hopeful About Clinical Trials of Adoptive Cell Transfer

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Updated July 31, 2009

Adoptive cell transfer (ACT) is an promising melanoma treatment that is currently in clinical trials. Why are doctors excited about it? The history of melanoma treatment, especially for people with advanced (stage III) or metastatic (stage IV) disease, has been marked by decades of failures and mediocre results. Along with several other emerging drugs, ACT is giving patients and doctors hope that an effective treatment for this devastating disease is on its way soon.

How Does ACT Work?

First, the person's own white blood cells (technically called autologous lymphocytes) are isolated in the laboratory from a blood sample. Next, the chemotherapy drugs cyclophosphamide and fludarabine are given to deplete most of the person's remaining lymphocytes. Meanwhile, the most aggressive tumor-killing lymphocytes are identified, multiplied in the lab, and then re-injected back into the patient. Finally, the person receives a high dose of interleukin-2, a protein made by the body that makes the tumor-fighting cells mature and multiply. The ACT method essentially "fine-tunes" the body's immune system to specifically attack an individual's own cancerous melanoma cells.

Does ACT Work?

In a 2005 study of 35 patients, led by Dr. Steven A. Rosenberg at the National Cancer Institute in Bethesda, Maryland, 18 (51%) experienced an improvement in the amount of tumor present at various sites in the body (lung, liver, lymph nodes, brain and skin). Eight other patients demonstrated a mixed or minor response. Of those who showed improvement, 15 had a partial response that lasted from two months to more than two years. It is especially noteworthy that there were three (9%) patients who continued to experience complete disappearance of their tumors. The overall response rates seen were far higher than the 10% to 15% response rates seen with other drugs approved for patients with metastatic melanoma (such as dacarbazine). This result is particularly significant because these patients had not responded to the standard chemotherapies or other treatments typically used in treating patients with melanoma.

An even more promising modification of this study was published in 2008. This time, instead of killing off the person's white blood cells only with chemotherapy drugs, whole-body radiation was added. Amazingly, response rates to ACT of up to 72% were observed in 93 patients.

Is It Safe?

Yes. There were no treatment-related deaths in the 2005 ACT study. However, the loss of white blood cells, which fight infections, led to the development of minor infections in seven patients. Other side effects related to the treatment were easily managed.

These studies demonstrate that, in some patients, the ACT method can impact metastatic melanoma growth and patient survival in ways that conventional therapy including surgery, radiotherapy, and chemotherapy cannot. However, two cautions need to be highlighted:

  • This method can only be used for melanoma patients who already have a population of specialized lymphocytes that recognize tumors as abnormal cells.
  • Many techniques and drugs in early clinical trials unfortunately fail in larger studies and aren't approved.
Although it's too early to claim it is a breakthrough, ACT is a very exciting development that patients and doctors should closely follow.

Sources:

Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. Journal of Clinical Oncology April 1, 2005; 23(10).

Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002; 298:850-854.

Dudley ME, Yang JC, Sherry R, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. Journal of Clinical Oncology. 2008 Nov 10;26(32):5233-9.

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