Gene Therapy Using Anti-CEA Cells to Treat Metastatic Cancer

Summary

Background: * Carcinoembryonic antigen (CEA) is a protein present mostly in cancer cells. * An experimental procedure developed for treating patients with cancer uses blood cells found in their tumors or bloodstream. These cells are genetically modified using the anti-CEA gene and a type of virus. The modified cells (anti-CEA cells) are grown in the laboratory and then given back to the patient to try to decrease the size of the tumors. This is called gene therapy. Objectives: * To determine whether advanced cancers that that express the CEA antigen can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-CEA protein. Eligibility: * Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site) and for whom standard treatments are not effective. * Patients' tumors express the CEA antigen. * Patients have the human leukocyte (HLA-A\*0201) antigen. Design: * Workup with scans, x-rays and other tests. * Leukapheresis to obtain cells for preparing the anti-CEA cells for later infusion. * 1 week of chemotherapy to prepare the immune system for receiving the anti-CEA cells. * Infusion of anti-CEA cells, followed by interleukin-2 (IL-2) treatment. The cells are given as an infusion through a vein. IL-2 is given as a 15-minute infusion through a vein every 8 hours for a maximum of 15 doses. * 1-2 weeks of recovery from the effects of chemotherapy and IL-2. * Periodic follow-up clinic visits after hospital discharge for physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.

Timeline

Start

2008-12

Primary completion

2011-11

Completion

2011-11

Publications

• Background Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850-4. doi: 10.1126/science.1076514. Epub 2002 Sep 19.
• Background Gattinoni L, Powell DJ Jr, Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol. 2006 May;6(5):383-93. doi: 10.1038/nri1842.
• Background Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ, Jones SA, Mangiameli DP, Pelletier MM, Gea-Banacloche J, Robinson MR, Berman DM, Filie AC, Abati A, Rosenberg SA. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005 Apr 1;23(10):2346-57. doi: 10.1200/JCO.2005.00.240.

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