(Phase I) 癌症T細胞治療 (CD4 T cells targeting MAGE-A3)

 CD4 T-Cell Immunotherapy Active in Various Cancers  News | April 19, 2016 | AACR 2016 By Anna Azvolinsky, PhD Results of a trial involving a CD4-based immunotherapy has shown activity in patients with metastatic solid tumors, according to phase I data presented at the 2016 American Association for Cancer Research (AACR) Annual Meeting, held April 16–20 in New Orleans."This is a very promising conceptual strategy and the early responses are exciting," said moderator Louis M. Weiner, MD, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, during a press conference. Fourteen patients with metastatic cancer were treated with the novel, individualized CD4 T cell–based therapy, and responses occurred in three patients with different cancer types—cervical, esophageal, and urothelial. The patient with cervical cancer has had an ongoing response for over 15 months. In the patient with esophageal cancer the response lasted 4 months, and the response in the patient with urothelial cancer has been ongoing for more than 7 months. The immunotherapy was derived from the patients' own blood, isolating CD4 T cells that were then genetically modified using a retrovirus to express a T cell–receptor specific for MAGE-A3. MAGE-A3 is an antigen that is expressed on many different tumor types but not generally expressed in normal tissue. The T cells were then propagated in the lab to generate a large population of the cells before transplanting these back into the patient. This is the first CD4-based, genetically engineered immunotherapy," study author Steven A. Rosenberg, MD, PhD, chief of the surgery branch at the National Cancer Institute in Bethesda, Maryland, told Cancer Network. "Any HLA-DPB0401 patient with metastatic cancer that homogeneously expresses MAGE-A3 is potentially eligible." The work is partly based on prior evidence from Rosenberg's lab that showed naturally occurring CD4 T cells can mediate an antitumor response. Other T cell–based immunotherapies currently in development involve CD8 T cells. All 14 patients received at least one dose (of several experimental escalating doses), with six patients treated at the highest dose of 100 billion cells. One month post-treatment, the six patients who received these higher doses had high levels of engineered T cells detectable in their blood compared with patients who received lower doses (10 million cells). The patients with cervical, esophageal, and urothelial cancers, who each had a partial response, were treated with doses of 2.7 billion, 100 billion, and 100 billion cells, respectively. The therapy was considered safe. Adverse events included high fever and high serum levels of cytokine IL-6, which were manageable. Based on the safety of the therapy, the authors have started a phase II trial to test the efficacy of the CD4 T cell-based therapy in other types of metastatic cancer.