Adoptive immunity may be the next major step forward in cancer treatment. Phase II trials at the National Cancer Institute have shown significant success in mediating the regression of established metastatic cancers, while plans for a phase III trial are currently under review at the Food and Drug Administration.
“We have seen dramatic regressions in patients with melanoma,” said Steven Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the National Cancer Institute in Bethesda, Maryland. “We’ve seen regressions in patients with sarcomas and lymphomas as well. We are looking at applications of adoptive T cell immunotherapy to the treatment of prostate cancer and kidney cancer. It’s a new way to treat cancer.”
Dr. Rosenberg will discuss the latest developments in adoptive T cell immunotherapy during the annual John K. Lattimer Lecture that concludes today’s opening Plenary Session. Dr. Rosenberg will present his lecture, New Approaches to Cancer Immunotherapy, from 11:40 a.m. – 12:00 p.m. in Hall D of the Walter E. Washington Convention Center.
Researchers are pursuing two approaches to adoptive immunotherapy, Dr. Rosenberg explained. One track uses autologous tumor infiltrating lymphocytes (TILs) that have been selected for antitumor activity. Selected TILs are cultured, expanded and infused back into the patient for treatment. Autologous transfusions are useful primarily in melanomas, the only histological tumor type that readily gives rise to TILs that have demonstrable antitumor activity.
Pilot trials showed objective response rates of 49 percent to 72 percent, Dr. Rosenberg reported. More than a fifth of patients, 22 percent, had complete regression of widespread cancer for up to 82 months.
The second track is an autologous T cell transfer technology that is commonly described as gene therapy. Genes encoding cytokines or antitumor T cell receptors (TCRs) are transduced into normal peripheral lymphocytes. The genetically engineered lymphocytes are cultured and transfused into the patient for treatment.
Antitumor TCRs that recognize the MART-1 and gp100 melanoma/melanocyte antigens, the NY-ESO-1 cancer-testis antigen and the carcinoembryonic antigen have all been identified. Researchers have also used chimeric antibody TCRs against CD19 expressed on B lymphoma cells. Similar cell transfer techniques are being developed to attack prostate and kidney cancers.
Early results are encouraging. A melanoma trial using MART-1 TCR produced an objective response rate of 30 percent. Clinical responses have also been seen in patients with synovial cell sarcoma and melanoma treated with anti-NY-ESO-1 TCR. Patients with B cell lymphoma have shown an objective response to the CD19 chimeric antibody TCR.
“The cellular and molecular mechanisms of precisely how T cells attack and destroy cancers are under active investigation,” Dr. Rosenberg said.
Adoptive immunotherapy is a new area for most clinicians, he noted. The first results from this approach to genetic engineering were published in 2006 from a small trial with just 13 patients. The trial in lymphoma was published in the Journal of Clinical Oncology in November 2010 and the sarcoma trial was published in Blood in March 2011.
“This is all very new,” Dr. Rosenberg said. “It is in aggressive clinical trials but is still highly experimental. It will be at least a couple of years until it moves into more common practice.”