Adoptive Cell Therapy for B-Cell Cancers in Patients After Stem Cell Transplantation

Summary

Background: * After allogeneic (donor) stem cell transplantation, a new immune system grows in the patient from the transplanted donor stem cells and lymphocytes (type of immune cell). Donor lymphocytes, unlike the patient s own lymphocytes, often can recognize the patient s tumor cells as being foreign and destroy them. * It is thought that tumor shrinkage after stem cell transplantation is the result of donor T lymphocytes, or T cells. Some studies show that patients with tumors that have T cells are better able to keep tumor growth in check. * Patients who have had donor stem cell transplantation may have donor T cells in their tumors that can recognize and fight their cancer. Compared with donor T cells taken directly from the donor and infused into the patient, donor T cells found in patients tumors may be specific for the cancer cells and thus better able to attack tumor. Also, because the T cells found their way to the tumor, they may be less likely to recognize and attack non-tumor tissues than the T cells given in donor lymphocyte infusions. * The T cells may be especially effective at controlling tumor if they are given an additional stimulus to become active. Costimulation is the name of the body s natural process for providing an extra stimulus, and can be performed on cells in the laboratory. Costimulation can produce large numbers of activated cells that may be able to attack cancer cells and shrink tumors. Objectives: -To evaluate the ability of lymphocytes found in tumors from patients who have received donor stem cell transplants to control their tumor growth. Eligibility: -Patients between 18 and 75 years of age with a B-cell cancer that has continued to grow or recurred after remission following allogeneic stem cell transplantation. This includes patients who have received transplants from unrelated donors and cord blood. Design: * Immune cells are collected from patients blood and blood from their stem cell donor. * Patients undergo surgery to remove their tumor and a small piece of skin. In the laboratory, donor T cells are isolated from the tumor and costimulated to expand the number of cells and activate them. * The expanded, activated T cells as infused into the patient. * Patients have a needle biopsy and possibly surgery to remove a sample of remaining tumor for research studies. * Patients are followed at the NIH clinic 48 hours after the cell infusion, and again at 1, 2, 4, 8 and 12 weeks after the infusion. Tumor size is monitored every month with CT scans, and possibly also with a PET or bone marrow aspiration and biopsy, for the first 3 months after the cells are infused. Thereafter, visits are less frequent (every 3 months, then every 6 months, and then yearly) during a minimum 5-year follow-up.

Timeline

Start

2007-01-11

Primary completion

2013-04-24

Completion

2013-04-24

Publications

• Background Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11810-3. doi: 10.1073/pnas.92.25.11810.
• Background Russell NH, Byrne JL, Faulkner RD, Gilyead M, Das-Gupta EP, Haynes AP. Donor lymphocyte infusions can result in sustained remissions in patients with residual or relapsed lymphoid malignancy following allogeneic haemopoietic stem cell transplantation. Bone Marrow Transplant. 2005 Sep;36(5):437-41. doi: 10.1038/sj.bmt.1705074.
• Background Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. doi: 10.1056/NEJM199304083281404.
• Hardy NM, Fellowes V, Rose JJ, Odom J, Pittaluga S, Steinberg SM, Blacklock-Schuver B, Avila DN, Memon S, Kurlander RJ, Khuu HM, Stetler-Stevenson M, Mena E, Dwyer AJ, Levine BL, June CH, Reshef R, Vonderheide RH, Gress RE, Fowler DH, Hakim FT, Bishop MR. Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation. Blood. 2012 Mar 22;119(12):2956-9. doi: 10.1182/blood-2011-09-378398. Epub 2012 Jan 30.

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