This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of this study is to assess the safety and feasibility of collecting T cells (blood cells that help fight infection) from subjects with a type of follicular lymphoma of B-cell origin, genetically modifying them in the laboratory to recognize this type of lymphoma cell, and infusing them (giving them back by vein) to the same subjects. In addition to assessing the safety of delivering lymphoma-specific T cells, the safety of using the hormone IL-2 to support the survival of the infused T cells will also be studied. This study will also try to determine how long these cells stay in the blood stream after re-infusion and if they attack lymphoma cells once they are inside the body. In this study, cells that are part of the immune system, called cytotoxic T lymphocytes (CTL) or T cells, will be collected from study subjects with follicular lymphoma of B cell origin. These T cells will then be genetically modified in the laboratory to kill follicular lymphoma cells of B cell origin. To do this, a piece of recombinant (artificial) DNA will be made in the laboratory and inserted into the T cells. This piece of recombinant DNA will allow the T cell to make a 'receptor' that recognizes CD19, a substance expressed by lymphoma cells of B cell origin. The number of genetically modified T cells will be expanded in the laboratory. The cells will undergo safety and quality assurance testing. The cells will also be tested to make sure they recognize CD19. After all of these steps have been completed, the genetically modified T cells will be infused intravenously (IV, by vein) into the subject from whom the T cells were originally collected. While these genetically modified T cells have been shown to kill tumor cells in the laboratory and in mice, it is not known whether they will work in a similar manner in humans. Normal B cells also express the CD19 molecule. B cells make a protein called immunoglobulin (Ig) that is important in fighting off infections. The genetically modified T cells are not capable of distinguishing a normal B cell from a lymphoma cell derived from a B cell. Therefore, the genetically modified T cells would be likely to target both types of cells. To lower the risk that the genetically modified T cells will attack normal B cells, subjects are given a single IV infusion of the commercially available drug rituximab before the first T cell infusion. Rituximab will lower the amount of both lymphoma cells derived from B cells and normal B cells (that would otherwise serve as targets for the genetically modified T cells). During the period of time that the number of B cells is lower, subjects who experience an infection may be given IVIg, a purified protein preparation of Ig obtained from healthy donors that can be given IV. In previous immunotherapy studies, subjects' immune systems generated a response against the genetically modified T cells that caused them to be destroyed early. Another reason for giving rituximab before the first T cell infusion is that it will lower the risk of such an immune response. In addition, beginning the fourth day after the first T cell infusion, subjects will also be given up to five daily infusions of fludarabine. Fludarabine is a commercially available chemotherapy agent that will also help lower the risk of an immune response. The hormone IL-2 will also be given by subcutaneous (under the skin) injection to help the genetically modified T cells survive for a longer period of time inside the subject's body.
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