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Induction of Tumor Dormancy In Balb/c Mice Against Nonimmunogenic B Cell Leukemia
Published in Thomas H. M. Stewart, E. Frederick Wheelock, Cellular Immune Mechanisms and Tumor Dormancy, 2017
Shimon Slavin, Aliza Ackerstein, Lola Weiss, Arnon Nagler, Reuven Or, Elizabeth Naparstek
Allogeneic BMT is the ultimate and most potent therapy available for a large variety of malignant hematological disorders that cannot be successfully treated with conventional chemotherapy. Allogeneic BMT provides the option of administration of maximal tolerated doses of chemoradiotherapy in an attempt to eliminate as many tumor cells as possible, regardless of the limiting factor of marrow toxicity, but in addition represents cellular adoptive immunotherapy of donor immunocompetent T lymphocytes and perhaps NK. cells against residual tumor cells of the host that have escaped chemoradiotherapy2'3. Comparisons in the rate of relapse of patients with acute or chronic leukemias treated by allogeneic BMT in comparison with syngeneic BMT, ABMT, or T cell depleted allografts (particularly when combined with post-transplant anti-GVHD immunosuppressive prophylaxis) suggest that GVL effects induced by the allograft are equally important to the effect of high dose chemoradiotherapy2,3. Although there seems to be no controversy as to the beneficial role of GVL effects in conjunction with allogeneic BMT, there still exists some controversy as to whether curative GVL effects may be induced independently of GVHD3. Although GVHD potential seems to be an important requisite for induction of GVL effects, previously published animal data8-10 and recent clinical observations2 indicate that GVL effects may be at least partly independent of GVHD3. Unequivocal evidence which points to the existence of GVL effects which may be independent of GVHD further encouraged continuation of investigations on the basic cell mediated mechanisms of GVHD and GVL in terms of effector cells involved11 or target epitopes recognized.
Novel agents positively impact chemotherapy and transplantation in Hodgkin lymphoma
Published in Expert Review of Hematology, 2019
Parastoo B. Dahi, Craig H. Moskowitz, Sergio A. Giralt, Hillard M. Lazarus
Cellular adoptive immunotherapy for virus-associated malignant disease is an attractive strategy, since viral antigens provide targets for T lymphocytes. In Epstein-Barr virus (EBV)-positive HL, a number of EBV-encoded antigens such as the latent membrane antigens (LMP) 1 and 2 are expressed on the malignant Reed-Sternberg cells. These tumor cells are infected by EBV in about 40% of the cases [64]. Studies have shown that some patients with relapsed EBV-associated HL enter CR after treatment with autologous EBV-specific cytotoxic T lymphocytes (CTLs) [65,66]. Bollard and colleagues investigated the role of EBV-specific CTLs in 50 patients with EBV-associated lymphomas. Twenty-five patients had HL, 11 had NK/T-cell non-Hodgkin lymphoma (NHL), 7 had diffuse large B-cell lymphoma (DLBCL), 2 had post-transplant lymphoproliferative disorder (PTLD), 1 had peripheral T-cell NHL, and 4 had other lymphomas. The 2-year EFS rate in the 29 patients who were treated in remission was 82%. Among 21 patients with active disease, 11 achieved durable CR, and 2 achieved PR. Overall, the 2-year EFS rate among patients treated for rel/ref disease was approximately 50%, with deaths evenly distributed between relapse and non-relapse causes [67]. At MSKCC, EBV+ lymphomas after alloHCT have been successfully treated with third-party EBV-CTLs [68]. Summary: Immunotherapeutic strategies with CD30 CAR T-cell and EBV-CTLs are attractive treatment strategies for rel/ref HL. Their use currently is under investigation.
Pharmacologic and immunologic management of cytomegalovirus infection after solid organ and hematopoietic stem cell transplantation
Published in Expert Review of Clinical Pharmacology, 2018
Atibordee Meesing, Raymund R. Razonable
However, cellular adoptive immunotherapy has been limited by availability, the long time to generate adequate cells for infusion, donor serostatus, and its personalized nature [125] [118].To curtail this limitation, the use of off-the-shelf, third-party virus-specific T cells that are active against CMV have been suggested and tested [126]. In a prospective study of 30 allogeneic HSCT patients, including 28 with persistent or recurrent CMV, infusion of partially HLA-matched, third-party, ex vivo-expanded virus-specific T cells (total = 50 infusions) was safe and well-tolerated. At 12 months, the cumulative incidence of overall response was 93%, and there was durable virological control in majority of patients [127] [111].