Adoptive Transfer

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Stanley R Riddell - One of the best experts on this subject based on the ideXlab platform.

  • Adoptive Transfer of virus specific and tumor specific t cell immunity
    Current Opinion in Immunology, 2009
    Co-Authors: Carolina Berger, Cameron J Turtle, Michael C Jensen, Stanley R Riddell
    Abstract:

    The Adoptive Transfer of T cells isolated or engineered to have specificity for diseased cells represents an ideal approach for the targeted therapy of human viral and malignant diseases. The therapeutic potential of Adoptive T cell therapy for infections and cancer was demonstrated in rodent models long ago, but the task of translating this approach into an effective clinical therapy has not been easy. Carefully designed clinical trials have evaluated the Transfer of antigen-specific T cells in humans, and provided insight into the barriers to efficacy and strategies to improve T cell therapy. The importance of altering the host environment to facilitate persistence and function of Transferred T cells and intrinsic properties of T cells that are selected or engineered for therapy in determining their fate in vivo are key issues that have recently emerged and are informing the design of the next generation of clinical trials.

  • Adoptive Transfer of effector cd8 t cells derived from central memory cells establishes persistent t cell memory in primates
    Journal of Clinical Investigation, 2008
    Co-Authors: Carolina Berger, Michael C Jensen, Peter M Lansdorp, Mike Gough, Carole Elliott, Stanley R Riddell
    Abstract:

    The Adoptive Transfer of antigen-specific T cells that have been expanded ex vivo is being actively pursued to treat infections and malignancy in humans. The T cell populations that are available for Adoptive immunotherapy include both effector memory and central memory cells, and these differ in phenotype, function, and homing. The efficacy of Adoptive immunotherapy requires that Transferred T cells persist in vivo, but identifying T cells that can reproducibly survive in vivo after they have been numerically expanded by in vitro culture has proven difficult. Here we show that in macaques, antigen-specific CD8+ T cell clones derived from central memory T cells, but not effector memory T cells, persisted long-term in vivo, reacquired phenotypic and functional properties of memory T cells, and occupied memory T cell niches. These results demonstrate that clonally derived CD8+ T cells isolated from central memory T cells are distinct from those derived from effector memory T cells and retain an intrinsic capacity that enables them to survive after Adoptive Transfer and revert to the memory cell pool. These results could have significant implications for the selection of T cells to expand or to engineer for Adoptive immunotherapy of human infections or malignancy.

  • selective reconstitution of cd8 cytotoxic t lymphocyte responses in immunodeficient bone marrow transplant recipients by the Adoptive Transfer of t cell clones
    Bone Marrow Transplantation, 1994
    Co-Authors: Stanley R Riddell, B A Walter, Mark J Gilbert, Philip D Greenberg
    Abstract:

    : The Adoptive Transfer of T cells specific for antigens encoded by pathogens and tumors has been an effective treatment for infections and malignancies in animal models and is potentially applicable for infections occurring in immunodeficient bone marrow transplant recipients. This article reviews recent insights derived from studies of the immunobiology of human cytomegalovirus (CMV) infection in healthy and immunodeficient hosts and the development of Adoptive immunotherapy as prophylaxis for CMV infection in recipients of allogeneic bone marrow transplants.

  • restoration of viral immunity in immunodeficient humans by the Adoptive Transfer of t cell clones
    Science, 1992
    Co-Authors: Stanley R Riddell, Kathe S Watanabe, James M Goodrich, Cheng R Li, Mounzer E Agha, Philip D Greenberg
    Abstract:

    The Adoptive Transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. The application of this approach to human disease would require the isolation and in vitro expansion of human antigen-specific T cells and evidence that such T cells persist and function in vivo after Transfer. Cytomegalovirus-specific CD8+ cytotoxic T cell (CTL) clones could be isolated from bone marrow donors, propagated in vitro, and Adoptively Transferred to immunodeficient bone marrow transplant recipients. No toxicity developed and the clones provided persistent reconstitution of CD8+ cytomegalovirus-specific CTL responses.

Akira Shimizu - One of the best experts on this subject based on the ideXlab platform.

  • Adoptive Transfer of renal allograft tolerance in a large animal model
    American Journal of Transplantation, 2016
    Co-Authors: Vincenzo Villani, Kazuhiko Yamada, Joseph R Scalea, B Gillon, M Sekijima, Masayuki Tasaki, Taylor Cormack, S Moran, Radbeh Torabi, Akira Shimizu
    Abstract:

    Our recent studies in an inbred swine model demonstrated that both peripheral and intra-graft regulatory cells were required for the Adoptive Transfer of tolerance to a second, naive donor-matched kidney. Here, we have asked whether both peripheral and intra-graft regulatory elements are required for Adoptive Transfer of tolerance when only a long-term tolerant (LTT) kidney is transplanted. Nine highly-inbred swine underwent a tolerance-inducing regimen to prepare LTT kidney grafts which were then transplanted to histocompatible recipients, with or without the peripheral cell populations required for Adoptive Transfer of tolerance to a naive kidney. In contrast to our previous studies, tolerance of the LTT kidney transplants alone was achieved without Transfer of additional peripheral cells and without strategies to increase the number/potency of regulatory T cells in the donor. This tolerance was systemic, since most subsequent, donor-matched challenge kidney grafts were accepted. These results confirm the presence of a potent tolerance-inducing and/or tolerance-maintaining cell population within LTT renal allografts. They suggest further that additional peripheral tolerance mechanisms, required for Adoptive Transfer of tolerance to a naive donor-matched kidney, depend on peripheral cells that, if not Transferred with the LTT kidney, require time to develop in the Adoptive host.

  • the induction of tolerance of renal allografts by Adoptive Transfer in miniature swine
    American Journal of Transplantation, 2013
    Co-Authors: Masayoshi Okumi, Vincenzo Villani, Joseph R Scalea, B Gillon, Masayuki Tasaki, Taylor Cormack, Akira Shimizu, Atsushi Hirakata, David H Sachs, Kazuhiko Yamada
    Abstract:

    Our previous in vitro data have demonstrated that regulatory mechanisms are involved in tolerance of class I-mismatched renal allografts in miniature swine treated with 12 days of high dose Cyclsporin A. In this study, we attempted to induce tolerance of class I-mismatched kidneys by Adoptive Transfer of cells and/or kidneys from long-term tolerant animals. Fifteen SLA dd miniature swine received 1.5 Gy whole body irradiation and class I-mismatched (SLA gg ) kid

  • renal allograft rejection is prevented by Adoptive Transfer of anergic t cells in nonhuman primates
    Journal of Clinical Investigation, 2005
    Co-Authors: Hisashi Bashuda, Akira Shimizu, Masaaki Kimikawa, Kenichiro Seino, Yojiro Kato, Hideo Yagita, Satoshi Teraoka, Ko Okumura
    Abstract:

    Anergic T cells generated ex vivo are reported to have immunosuppressive effects in vitro and in vivo. Here, we tested this concept in nonhuman primates. Alloreactive T cells were rendered anergic ex vivo by coculture with donor alloantigen in the presence of anti-CD80/CD86 mAbs before Adoptive Transfer via renal allograft to rhesus monkey recipients. The recipients were briefly treated with cyclophosphamide and cyclosporine A during the preparation of the anergic cells. Thirteen days after renal transplantation, the anergic T cells were Transferred to the recipient, after which no further immunosuppressive agents were administered. Rejection-free survival was prolonged in all treated recipients, and 3 of 6 animals survived long term (410–880 days at study’s end). In the long-surviving recipients, proliferative responses against alloantigen were inhibited in a donor-specific manner, and donor-type, but not third-party, skin allografts were also accepted, which demonstrated that antigen-specific tolerance had been induced. We conclude that anergic T cells generated ex vivo by blocking CD28/B7 costimulation can suppress renal allograft rejection after Adoptive Transfer in nonhuman primates. This strategy may be applicable to the design of safe clinical trials in humans.

Robert Beck - One of the best experts on this subject based on the ideXlab platform.

  • safe Adoptive Transfer of virus specific t cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation
    British Journal of Haematology, 2006
    Co-Authors: Tobias Feuchtinger, Susanne Matthesmartin, Celine Richard, Thomas Lion, Monika Fuhrer, Klaus Hamprecht, Rupert Handgretinger, Christina Peters, Friedhelm R Schuster, Robert Beck
    Abstract:

    : During periods of immunosuppression, such as postallogeneic stem cell transplantation (SCT), patients are at significant risk for severe viral infections. Human adenovirus (HAdV) infection is a serious complication post-SCT, especially in children. Virus-specific T cells are essential for the clearance of HAdV, as antiviral chemotherapy has revealed limited success. We present feasibility data for a new treatment option using virus-specific donor T cells for Adoptive Transfer of immunity to patients with HAdV-infection/reactivation. Virus-specific donor T cells were isolated and infused into nine children with systemic HAdV infection after SCT. Isolation was based on gamma-interferon (IFN-gamma) secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4(+) and CD8(+) T cells. 1.2-50 x 10(3)/kg T cells were infused for Adoptive Transfer. Isolated cells showed high specificity and markedly reduced alloreactivity in vitro. Adoptive Transfer of HAdV-specific immunity was successful in five of six evaluable patients, documented by a dose-independent and sustained in vivo expansion of HAdV-specific T cells, associated with a durable clearance/decrease of viral copies. T-cell infusion was well tolerated in all nine patients, except one case with graft-versus-host disease II of the skin. In conclusion, induction of a specific T-cell response through Adoptive Transfer was feasible and effective. When performed early in the course of infection, Adoptive T-cell Transfer may protect from HAdV-related complications.

Mark E Dudley - One of the best experts on this subject based on the ideXlab platform.

  • randomized prospective evaluation comparing intensity of lymphodepletion before Adoptive Transfer of tumor infiltrating lymphocytes for patients with metastatic melanoma
    Journal of Clinical Oncology, 2016
    Co-Authors: Stephanie L Goff, Mark E Dudley, John R Wunderlich, James Chihhsin Yang, Richard M Sherry, Deborah Citrin, Robert Somerville, David N Danforth, Daniel Zlott, Udai S Kammula
    Abstract:

    PurposeAdoptive cell Transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the Adoptive Transfer of tumor-infiltrating lymphocytes (TIL) in a randomized fashion.Patients and MethodsA total of 101 patients with metastatic melanoma, including 76 patients with M1c disease, were randomly assigned to receive nonmyeloablative chemotherapy with or without 1,200 cGy TBI before Transfer of tumor-infiltrating lymphcytes. Primary end points were CR rate (as defined by Response Evaluation Criteria in Solid Tumors v1.0) and overall survival (OS). Clinical and laboratory data were analyzed for correlates of response.ResultsCR rates were 24% in bo...

  • generation of tumor infiltrating lymphocyte cultures for use in Adoptive Transfer therapy for melanoma patients
    Journal of Immunotherapy, 2003
    Co-Authors: Mark E Dudley, John R Wunderlich, Thomas E Shelton, Jos Even, Steven A. Rosenberg
    Abstract:

    The generation of T lymphocytes with specific reactivity against tumor antigens is a prerequisite for effective Adoptive Transfer therapies. Melanoma-specific lymphocyte cultures can be established from tumor infiltrating lymphocytes (TILs) by in vitro culture in high levels of IL-2. We have optimized methods for generating melanoma-reactive TIL cultures from small resected tumor specimens. We report a retrospective analysis of 860 attempted TIL cultures from 90 sequential melanoma biopsy specimens from 62 HLA-A2+ patients. Multiple independent TIL derived from a single tumor often exhibited substantial functional and phenotypic variation. Tumor specific activity was detected in TIL from 29 (81%) of 36 patients screened. TIL cultures selected for high activity were generally capable of large numerical expansion using a single round of a rapid expansion protocol. Limited clonal T-cell populations in an oligoclonal TIL culture could confer specific tumor recognition in these highly selected, highly expanded TIL cultures. These methods were efficient at generating TILs suitable for Adoptive Transfer therapy.

Kazuhiko Yamada - One of the best experts on this subject based on the ideXlab platform.

  • Adoptive Transfer of renal allograft tolerance in a large animal model
    American Journal of Transplantation, 2016
    Co-Authors: Vincenzo Villani, Kazuhiko Yamada, Joseph R Scalea, B Gillon, M Sekijima, Masayuki Tasaki, Taylor Cormack, S Moran, Radbeh Torabi, Akira Shimizu
    Abstract:

    Our recent studies in an inbred swine model demonstrated that both peripheral and intra-graft regulatory cells were required for the Adoptive Transfer of tolerance to a second, naive donor-matched kidney. Here, we have asked whether both peripheral and intra-graft regulatory elements are required for Adoptive Transfer of tolerance when only a long-term tolerant (LTT) kidney is transplanted. Nine highly-inbred swine underwent a tolerance-inducing regimen to prepare LTT kidney grafts which were then transplanted to histocompatible recipients, with or without the peripheral cell populations required for Adoptive Transfer of tolerance to a naive kidney. In contrast to our previous studies, tolerance of the LTT kidney transplants alone was achieved without Transfer of additional peripheral cells and without strategies to increase the number/potency of regulatory T cells in the donor. This tolerance was systemic, since most subsequent, donor-matched challenge kidney grafts were accepted. These results confirm the presence of a potent tolerance-inducing and/or tolerance-maintaining cell population within LTT renal allografts. They suggest further that additional peripheral tolerance mechanisms, required for Adoptive Transfer of tolerance to a naive donor-matched kidney, depend on peripheral cells that, if not Transferred with the LTT kidney, require time to develop in the Adoptive host.

  • the induction of tolerance of renal allografts by Adoptive Transfer in miniature swine
    American Journal of Transplantation, 2013
    Co-Authors: Masayoshi Okumi, Vincenzo Villani, Joseph R Scalea, B Gillon, Masayuki Tasaki, Taylor Cormack, Akira Shimizu, Atsushi Hirakata, David H Sachs, Kazuhiko Yamada
    Abstract:

    Our previous in vitro data have demonstrated that regulatory mechanisms are involved in tolerance of class I-mismatched renal allografts in miniature swine treated with 12 days of high dose Cyclsporin A. In this study, we attempted to induce tolerance of class I-mismatched kidneys by Adoptive Transfer of cells and/or kidneys from long-term tolerant animals. Fifteen SLA dd miniature swine received 1.5 Gy whole body irradiation and class I-mismatched (SLA gg ) kid