Genomes and Genes
graft vs tumor effect
Summary: Immunological rejection of tumor tissue/cells following bone marrow transplantation.
- Inoue M, Nakano T, Yoneda A, Nishikawa M, Nakayama M, Yumura Yagi K, et al. Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transplant. 2003;32:103-6 pubmed..This case demonstrates the possibility of a graft-versus-tumor effect against neuroblastoma by HLA-mismatched allogeneic hematopoietic stem cell transplantation. ..
- Kanold J, Paillard C, Tchirkov A, Merlin E, Marabelle A, Lutz P, et al. Allogeneic or haploidentical HSCT for refractory or relapsed solid tumors in children: toward a neuroblastoma model. Bone Marrow Transplant. 2008;42 Suppl 2:S25-30 pubmed publisher..However, the proper timing for allo-HSCT during the disease course remains to be determined. ..
- Ash S, Gigi V, Askenasy N, Fabian I, Stein J, Yaniv I. Graft versus neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD. Cancer Immunol Immunother. 2009;58:2073-84 pubmed publisher..3) An effective GVT reaction in tumor bearing mice is primed by MHC disparity and targets tumor associated antigens. ..
- Ash S, Stein J, Askenasy N, Yaniv I. Immunomodulation with dendritic cells and donor lymphocyte infusion converge to induce graft vs neuroblastoma reactions without GVHD after allogeneic bone marrow transplantation. Br J Cancer. 2010;103:1597-605 pubmed publisher..Simultaneous inoculation of tumour-pulsed donor DC and DLI synergise in stimulation of potent GVT reactions to the extent of eradication of established NB tumours. ..
- Lokhorst H, Schattenberg A, Cornelissen J, Van Oers M, Fibbe W, Russell I, et al. Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol. 2000;18:3031-7 pubmed..Adjuvant DLI seems an attractive and promising approach for patients who do not achieve a molecular remission after AlloSCT. ..
- Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000;343:750-8 pubmed..Nonmyeloablative allogeneic stem-cell transplantation can induce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy. ..
- Teshima T, Mach N, Hill G, Pan L, Gillessen S, Dranoff G, et al. Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell-depleted bone marrow transplantation. Cancer Res. 2001;61:162-71 pubmed
- Le Blanc R, Montminy Métivier S, Belanger R, Busque L, Fish D, Roy D, et al. Allogeneic transplantation for multiple myeloma: further evidence for a GVHD-associated graft-versus-myeloma effect. Bone Marrow Transplant. 2001;28:841-8 pubmed..More importantly, our study clearly demonstrates an association between cGVHD and CR and brings further evidence in favor of a graft-versus-myeloma effect. ..
- Lang P, Pfeiffer M, Muller I, Schumm M, Ebinger M, Koscielniak E, et al. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr. 2006;218:321-6 pubmed..This approach may form the basis for posttransplant immunomodulation and other therapeutic strategies. Further experience is warranted to evaluate the method. ..
- Busca A, Novarino A, De Fabritiis P, Picardi A, Zeuli M, Locatelli F, et al. Nonmyeloablative allogeneic blood stem cell transplantation in patients with metastatic solid tumors. Hematology. 2006;11:171-7 pubmed..Careful patient selection seems to be mandatory in this transplant setting. ..
- Gill S, Porter D. Reduced-intensity hematopoietic stem cell transplants for malignancies: harnessing the graft-versus-tumor effect. Annu Rev Med. 2013;64:101-17 pubmed publisher..Reduced intensity has allowed a potentially curative therapy for hematologic malignancies to be offered to an expanded patient population. Ongoing research seeks to enhance the safety and power of this form of allogeneic immunotherapy. ..
- Fowler D. Shared biology of GVHD and GVT effects: potential methods of separation. Crit Rev Oncol Hematol. 2006;57:225-44 pubmed..Future success in this endeavor will require a strong commitment towards translational research and continued advances in cell, vaccine, cytokine, monoclonal antibody, and targeted molecular therapy. ..
- Stelljes M, Strothotte R, Pauels H, Poremba C, Milse M, Specht C, et al. Graft-versus-host disease after allogeneic hematopoietic stem cell transplantation induces a CD8+ T cell-mediated graft-versus-tumor effect that is independent of the recognition of alloantigenic tumor targets. Blood. 2004;104:1210-6 pubmed..It may represent one of the mechanisms contributing to GvT effects observed in allogeneic transplant recipients. ..
- Kahata K, Hashino S, Takahata M, Fujisawa F, Kondo T, Kobayashi S, et al. Durable remission of Sézary syndrome after unrelated bone marrow transplantation by reduced-intensity conditioning. Acta Haematol. 2008;120:14-8 pubmed publisher..Allogeneic hematopoietic stem cell transplantation, especially by reduced-intensity conditioning, is expected to become a curative treatment option, and graft-versus-tumor effect might play a critical role for sustained remission. ..
- Gahrton G. Risk assessment in haematopoietic stem cell transplantation: impact of donor-recipient sex combination in allogeneic transplantation. Best Pract Res Clin Haematol. 2007;20:219-29 pubmed..These results support the view that donor T cells specific for male minor histocompatiblity antigens encoded by Y-chromosome genes contribute to GVHD, graft rejection, GVT and survival in sex-mismatched transplants. ..
- Ueno N, Rizzo J, Demirer T, Cheng Y, Hegenbart U, Zhang M, et al. Allogeneic hematopoietic cell transplantation for metastatic breast cancer. Bone Marrow Transplant. 2008;41:537-45 pubmed..These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer. ..
- Anderlini P, Acholonu S, Okoroji G, Andersson B, Couriel D, De Lima M, et al. Donor leukocyte infusions in relapsed Hodgkin's lymphoma following allogeneic stem cell transplantation: CD3+ cell dose, GVHD and disease response. Bone Marrow Transplant. 2004;34:511-4 pubmed..The small sample size does not allow any conclusion as to whether chemotherapy administration increases the chance of response. The CD3 cell dose infused does not seem to correlate with disease response. ..
- Khan S, Gaa B, Pollock B, Shea B, Reddy V, Wingard J, et al. Engraftment syndrome in breast cancer patients after stem cell transplantation is associated with poor long-term survival. Biol Blood Marrow Transplant. 2001;7:433-8 pubmed..Thus, patients with ES should be considered for close follow-up and further therapy posttransplantation. ..
- Grigg A, Ritchie D. Graft-versus-lymphoma effects: clinical review, policy proposals, and immunobiology. Biol Blood Marrow Transplant. 2004;10:579-90 pubmed
- Feinstein L, Storb R. Reducing transplant toxicity. Curr Opin Hematol. 2001;8:342-8 pubmed..If long-term efficacy is demonstrated, such strategies will expand the options for patients who would not qualify for conventional allogeneic transplants. ..
- Espinoza Delgado I, Childs R. Nonmyeloablative transplantation for solid tumors: a new frontier for allogeneic immunotherapy. Expert Rev Anticancer Ther. 2004;4:865-75 pubmed..The development of strategies to decrease graft-versus-host disease while enhancing post-transplant antitumor immunity will hopefully be forthcoming in the near future. ..
- Schmaltz C, Alpdogan O, Kappel B, Muriglan S, Rotolo J, Ongchin J, et al. T cells require TRAIL for optimal graft-versus-tumor activity. Nat Med. 2002;8:1433-7 pubmed..These data suggest that strategies to enhance TRAIL-mediated GVT activity could decrease relapse rates of malignancies after hematopoietic cell transplantation without exacerbation of graft-versus-host disease. ..
- Peggs K, Mackinnon S, Williams C, D Sa S, Thuraisundaram D, Kyriakou C, et al. Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. Biol Blood Marrow Transplant. 2003;9:257-65 pubmed..Attempts to hasten immune reconstitution and to focus and amplify appropriate components of allogeneic T-cell responses will be required to increase complete remission rates and response durations. ..
- Kami M, Takaue Y. Development of reduced-intensity hematopoietic stem cell transplantation in the National Cancer Center Hospital, Japan. Ther Apher Dial. 2003;7:318-28 pubmed..However, the mechanism of graft-versus-host disease and graft-versus-tumor remains unclear. More knowledge on the mechanism is crucial to enhance antitumor effect and to further improve the prognosis. ..
- Ueno N, Shpall E, Champlin R, Jones R. Graft--versus--breast cancer effect by allogeneic hematopoietic stem-cell transplantation: a possible new frontier. J Clin Oncol. 2004;22:3846-7 pubmed
- Dean R, Bishop M. Allogeneic hematopoietic stem cell transplantation for lymphoma. Clin Lymphoma. 2004;4:238-49 pubmed..Patients with lymphoma should be selected for allogeneic HSCT on the basis of characteristics that strongly influence transplant outcomes, including histology, chemosensitivity, and donor source. ..
- Baurmann H, Nagel S, Binder T, Neubauer A, Siegert W, Huhn D. Kinetics of the graft-versus-leukemia response after donor leukocyte infusions for relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. Blood. 1998;92:3582-90 pubmed..This response pattern was confirmed by retrospective RT-PCR analysis in an additional five patients. Prospective monitoring of stem cell chimerism and response may enable us to individually tailor adoptive immunotherapy in the future. ..
- Oostvogels R, Lokhorst H, Mutis T. Minor histocompatibility Ags: identification strategies, clinical results and translational perspectives. Bone Marrow Transplant. 2016;51:163-71 pubmed publisher..Finally, we will outline the current challenges and future prospectives in the field. ..
- Valcarcel D, Martino R, Piñana J, Sierra J. Allogeneic stem cell transplantation after reduced-intensity conditioning for acute myeloid leukaemia: impact of chronic graft-versus-host disease. Curr Opin Oncol. 2009;21 Suppl 1:S35-7 pubmed publisher..For this purpose, an adequate identification of high-risk patients, close monitoring of minimal residual disease after the procedure, and the use of antineoplastic drugs or immunotherapy may be of help. ..
- Tsirigotis P, Or R, Resnick I, Shapira M. Immunotherapeutic approaches to improve graft-versus-tumor effect and reduce graft-versus-host disease. Immunotherapy. 2012;4:407-24 pubmed publisher..A brief description of these efforts is discussed in this review. ..
- Drachenberg D, Childs R. Allogeneic stem cell transplantation as immunotherapy for renal cell carcinoma: from immune enhancement to immune replacement. Urol Clin North Am. 2003;30:611-22 pubmed
- Farina L, Corradini P. Current role of allogeneic stem cell transplantation in follicular lymphoma. Haematologica. 2007;92:580-2 pubmed
- Müller A, Ihorst G, Waller C, Dölken G, Finke J, Engelhardt M. Intensive chemotherapy with autologous peripheral blood stem cell transplantation during a 10-year period in 64 patients with germ cell tumor. Biol Blood Marrow Transplant. 2006;12:355-65 pubmed..Our data suggest that auto-PBSCT can increase response rates and may improve the outcome in these patients. ..
- Galimberti S, Benedetti E, Morabito F, Fazzi R, Pacini S, Andreazzoli F, et al. Chimerism does not influence graft-versus-myeloma and graft-versus-host disease in reduced intensity setting. Transpl Immunol. 2005;15:173-7 pubmed..Moreover, even as result of a single center experience, we suggest that chimerism, graft-versus-myeloma and GVHD would represent distinct entities that require larger immunological studies for further clarification. ..
- Kline J, Subbiah S, Lazarus H, van Besien K. Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance. Bone Marrow Transplant. 2008;41:505-13 pubmed..New strategies to exploit auto-GVHD and enhance a GVM effect such as through the depletion of regulatory T cells or through use of newer immunomodulatory agents may improve the efficacy of auto-HCT. ..
- Le N, Chao N. Regulating regulatory T cells. Bone Marrow Transplant. 2007;39:1-9 pubmed..Their role in the development of GVHD and their therapeutic potential for the prevention and treatment of GVHD will also be described. ..
- Zeiser R, Finke J. Allogeneic haematopoietic cell transplantation for multiple myeloma: reducing transplant-related mortality while harnessing the graft-versus-myeloma effect. Eur J Cancer. 2006;42:1601-11 pubmed..Strategies including donor lymphocyte infusions as part of the allogeneic protocol and antigenic targets for GVM effect are reviewed. ..
- Porter D, Stadtmauer E, Lazarus H. 'GVHD': graft-versus-host disease or graft-versus-Hodgkin's disease? An old acronym with new meaning. Bone Marrow Transplant. 2003;31:739-46 pubmed..Nonmyeloablative conditioning and allogeneic SCT may induce a direct GVHL reaction with less conditioning regimen-related toxicity and ultimately may have the potential to improve cure rates and survival for advanced HL patients. ..
- Kogel K, McSweeney P. Reduced-intensity allogeneic transplantation for lymphoma. Curr Opin Oncol. 2002;14:475-83 pubmed..Controlled trials involving patients with earlier-stage disease appear warranted to define better the role of reduced-intensity allogeneic transplants in treating lymphomas. ..
- Kroger N, Kruger W, Renges H, Zabelina T, Stute N, Jung R, et al. Donor lymphocyte infusion enhances remission status in patients with persistent disease after allografting for multiple myeloma. Br J Haematol. 2001;112:421-3 pubmed..host disease (GvHD) and limited or extensive chronic GvHD in each patient. We conclude that DLI induced further tumour reduction in patients with persistent disease after allografting for multiple myeloma. ..
- Chia W, Wang W, Lim W, Tai W, Sun L, Thng C, et al. Nonmyeloablative allogeneic stem cell transplantation for nasopharyngeal carcinoma. Oncologist. 2010;15:1192-7 pubmed publisher..We also present data from a flow cytometric immune analysis and cytokine enzyme-linked immunosorbent assay analysis in the pre- and post-NST period. ..
- Jagasia M, Clark W, Brown Gentry K, Crawford D, Fan K, Chen H, et al. Genetic variation in donor CTLA-4 regulatory region is a strong predictor of outcome after allogeneic hematopoietic cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2012;18:1069-75 pubmed publisher..10-2.71, P = .017) and OS (HR = 1.84, 95% CI 1.13-3.0, P = .015). CTLA-4 SNPs can be used to identify high-risk patient subsets that may benefit from preemptive immunomodulation to decrease relapse rates and improve survival. ..
- Storb R, Gyurkocza B, Storer B, Sorror M, Blume K, Niederwieser D, et al. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2013;31:1530-8 pubmed publisher..Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD. ..
- Bensinger W. The current status of hematopoietic stem cell transplantation for multiple myeloma. Clin Adv Hematol Oncol. 2004;2:46-52 pubmed
- Hashimoto D, Merad M. Harnessing dendritic cells to improve allogeneic hematopoietic cell transplantation outcome. Semin Immunol. 2011;23:50-7 pubmed publisher..In this review, we summarize recent progress and potential new therapeutic avenues using dendritic cell-based strategies to improve allogeneic HCT outcome. ..
- Wang L, Liu J, Talebian F, El Omrani H, Khattabi M, Yu L, et al. Tumor expression of CD200 inhibits IL-10 production by tumor-associated myeloid cells and prevents tumor immune evasion of CTL therapy. Eur J Immunol. 2010;40:2569-79 pubmed publisher..Thus, tumor expression of CD200 prevents tumor recurrence via inhibiting IL-10 production by TAMC...
- Ando T, Yujiri T, Tominaga T, Shinya S, Takahashi T, Nomiyama J, et al. Autografting followed by a reduced-intensity conditioning unrelated donor cord blood transplantation for a patient with refractory multiple myeloma: successful engraftment with minimal toxicity. Eur J Haematol. 2005;74:175-9 pubmed..Although he had local recurrence in the right calf on day +130 after the CB transplantation, the tumor was successfully treated with radiation therapy, and he is alive and well at present (day +480). ..
- Srinivasan R, Barrett J, Childs R. Allogeneic stem cell transplantation as immunotherapy for nonhematological cancers. Semin Oncol. 2004;31:47-55 pubmed..The historical basis, development, and preliminary clinical results of allogeneic stem cell transplantation as a form of immunotherapy for treatment refractory solid tumors are reviewed. ..
- Orsini E, Bellucci R, Alyea E, Schlossman R, Canning C, McLaughlin S, et al. Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion. Cancer Res. 2003;63:2561-8 pubmed..In contrast, T-cell clones associated with GVHD are expanded de novo after DLI. ..
- Niederwieser D. [Allogeneic hematopoetic cell transplantation in patients with solid tumors - Pro]. Dtsch Med Wochenschr. 2002;127:2214 pubmed
- Kurokawa T, Fischer K, Bertz H, Hoegerle S, Finke J, Mackensen A. In vitro and in vivo characterization of graft-versus-tumor responses in melanoma patients after allogeneic peripheral blood stem cell transplantation. Int J Cancer. 2002;101:52-60 pubmed
- Clave E, Molldrem J, Hensel N, Raptis A, Barrett A. Donor-recipient polymorphism of the proteinase 3 gene: a potential target for T-cell alloresponses to myeloid leukemia. J Immunother. 1999;22:1-6 pubmed..These data support the possibility that T-cell responses to allelic differences of proteinase 3 could be used as a basis for designing leukemia-specific adoptive T-cell therapy in acute and chronic myeloid leukemias. ..