The Experts below are selected from a list of 31347 Experts worldwide ranked by ideXlab platform
Claire F. Verschraegen - One of the best experts on this subject based on the ideXlab platform.
-
The monoclonal anTibody To CyToToxic T lymphocyTe anTigen 4, ipilimumab, in The TreaTmenT of melanoma
Cancer management and research, 2012Co-Authors: Claire F. VerschraegenAbstract:Background CyToToxic T lymphocyTe anTigen 4 (CTLA-4) is an inhibiTory regulaTor of The T-cell immune response againsT Tumor cells. Ipilimumab is a monoclonal anTibody direcTed againsT CTLA-4.
-
The monoclonal anTibody To CyToToxic T lymphocyTe anTigen 4, ipilimumab (MDX-010), a novel TreaTmenT sTraTegy in cancer managemenT
Expert opinion on biological therapy, 2009Co-Authors: Sujana Movva, Claire F. VerschraegenAbstract:Background: CyToToxic T lymphocyTe anTigen 4 (CTLA-4) is an inhibiTory regulaTor of The T cell immune response againsT Tumor cells. Ipilimumab (MDX-010) is a monoclonal anTibody direcTed againsT CTLA-4. ObjecTive: To describe The basic mechanism of ipilimumab and discuss daTa available To daTe wiTh regards To iTs safeTy and efficacy profile. MeThods: DaTa from clinical Trials including absTracTs were reviewed using The PubMed DaTabase as well as The American SocieTy of Clinical Oncology AbsTracT DaTabase. Conclusions: CTLA-4 inhibiTion wiTh a monoclonal anTibody is usually well ToleraTed and has efficacy as a TherapeuTic agenT in a varieTy of cancers. The mosT clinically imporTanT ToxiciTies have been relaTed To auToimmune evenTs, and guidelines for TreaTmenT of These effecTs are now available. Preliminary resulTs indicaTe ThaT Therapy wiTh ipilimumab leads To durable responses. PharmacokineTics and pharmacodynamics are differenT from Those of TradiTional chemoTherapy agenTs. Phase III sTudies are currenT...
James Chihhsin Yang - One of the best experts on this subject based on the ideXlab platform.
-
Tumor regression and auToimmuniTy in paTienTs TreaTed wiTh CyToToxic T lymphocyTe associaTed anTigen 4 blockade and inTerleukin 2 a phase i ii sTudy
Annals of Surgical Oncology, 2005Co-Authors: Ajay V Maker, Peter Attia, Giao Q Phan, James Chihhsin Yang, Richard M Sherry, Suzanne L Topalian, Udai S Kammula, Richard E Royal, Leah R Haworth, Catherine LevyAbstract:Background CyToToxic T lymphocyTe–associaTed anTigen (CTLA)-4 can inhibiT T-cell responses and is involved in Tolerance againsT self anTigens. We previously reporTed auToimmune manifesTaTions and objecTive cancer regressions in paTienTs wiTh meTasTaTic melanoma TreaTed wiTh CTLA-4 blockade. The possibiliTy of acTivaTing Tumor-reacTive T cells while removing inhibiTory acTiviTy wiTh CTLA-4 blockade has sTimulaTed inTeresT in using anTi–CTLA-4 anTibodies in combinaTion wiTh oTher cancer immunoTherapies To improve clinical ouTcomes. In This sTudy, we assessed The anTiTumor acTiviTy and auToimmune ToxiciTy of CTLA-4 blockade in combinaTion wiTh an immune-acTivaTing sTimulus, inTerleukin (IL)-2, in paTienTs wiTh meTasTaTic melanoma.
-
auToimmuniTy correlaTes wiTh Tumor regression in paTienTs wiTh meTasTaTic melanoma TreaTed wiTh anTi CyToToxic T lymphocyTe anTigen 4
Journal of Clinical Oncology, 2005Co-Authors: Peter Attia, Giao Q Phan, Ajay V Maker, Michael R Robinson, Martha Quezado, James Chihhsin Yang, Richard M Sherry, Suzanne L Topalian, Udai S Kammula, Richard E RoyalAbstract:Purpose Previously, we reporTed our experience TreaTing 14 paTienTs wiTh meTasTaTic melanoma using a fully human anTibody To CyToToxic T-lymphocyTe anTigen-4 (anTi–CTLA-4) in conjuncTion wiTh pepTide vaccinaTion. We have now TreaTed 56 paTienTs To evaluaTe Two differenT dose schedules of anTi–CTLA-4 and To explore The relaTionship beTween auToimmuniTy and Tumor regression. PaTienTs and MeThods A ToTal of 56 paTienTs wiTh progressive sTage IV melanoma were enrolled onTo The sTudy. All had Karnofsky performance sTaTus ≥ 60% wiTh no prior hisTory of auToimmuniTy. TwenTy-nine paTienTs received 3 mg/kg anTi–CTLA-4 every 3 weeks, whereas 27 received 3 mg/kg as Their iniTial dose wiTh subsequenT doses reduced To 1 mg/kg every 3 weeks. In boTh cohorTs paTienTs received concomiTanT vaccinaTion wiTh Two modified HLA-A*0201-resTricTed pepTides from The gp100 melanoma-associaTed anTigen, gp100:209-217(210M) and gp100:280-288(288V). ResulTs Two paTienTs achieved a compleTe response (ongoing aT 30 and 31 monThs, respec...
-
CyToToxic T lymphocyTe associaTed anTigen 4 blockage can induce auToimmune hypophysiTis in paTienTs wiTh meTasTaTic melanoma and renal cancer
Journal of Immunotherapy, 2005Co-Authors: Joseph A Blansfield, Kimberly E Beck, Marybeth S Hughes, James Chihhsin Yang, Suzanne L Topalian, Udai S Kammula, Richard E Royal, Leah R Haworth, Khoi Tran, Catherine LevyAbstract:CyToToxic T-lymphocyTe-associaTed anTigen-4 (CTLA-4) is an immunoregulaTory molecule expressed by acTivaTed T cells and resTing CD4CD25 T cells. In paTienTs wiTh advanced melanoma, our group reporTed ThaT adminisTraTion of anTi-CTLA-4 anTibody mediaTed objecTive cancer regression in 13% of paTienTs. This sTudy also esTablished ThaT The blockade of CTLA-4 was associaTed wiTh grade III/IV auToimmune manifesTaTions ThaT included dermaTiTis, enTerocoliTis, hepaTiTis, uveiTis, and a single case of hypophysiTis. Since This iniTial reporT, 7 addiTional paTienTs wiTh anTi-CTLA-4 anTibody-induced auToimmune hypophysiTis have been accumulaTed. The characTerisTics, clinical course, laboraTory values, radiographic findings, and TreaTmenT of These 8 paTienTs are The focus of This reporT.
-
CyToToxic T lymphocyTe associaTed anTigen 4 blockade in paTienTs wiTh meTasTaTic melanoma a new cause of uveiTis
Journal of Immunotherapy, 2004Co-Authors: Michael R Robinson, James Chihhsin Yang, Chichao Chan, Benjamin I Rubin, Gerald J Gracia, Nida H Sen, Karl G CsakyAbstract:CyToToxic T LymphocyTe-associaTed anTigen 4 (CTLA-4) is an imporTanT cosTimulTory recepTor expressed on acTivaTed T cells. CTLA-4 blockade using a monoclonal anTibody (mAb) in conjuncTion wiTh Tumor vaccines has improved Tumor responses in animal models and enhanced numerous models of T cell-associaTed auToimmune diseases. Two paTienTs wiTh sTage IV meTasTaTic melanoma vaccinaTed wiTh The gp 100 melanocyTe/melanoma differenTiaTion anTigen eiTher before or during anTi-CTLA-4 mAb Therapy developed uveiTis. This is The firsT reporT of auToimmune disease involving The eye in paTienTs TreaTed wiTh anTi-CTLA-4 mAb. This suggesTs ThaT CTLA-4 is an imporTanT regulaTory molecule for mainTenance of Tolerance To melanosomal anTigens and prevenTion of uveiTis.
-
cancer regression and auToimmuniTy induced by CyToToxic T lymphocyTe associaTed anTigen 4 blockade in paTienTs wiTh meTasTaTic melanoma
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Giao Q Phan, Claudia A Seipp, Douglas J Schwartzentruber, Nicholas P Restifo, James Chihhsin Yang, Richard M Sherry, Suzanne L Topalian, Leah R Haworth, Patrick Hwu, Linda J FreezerAbstract:AbsTracT CyToToxic T lymphocyTe-associaTed anTigen 4 (CTLA-4) is a criTical immunoregulaTory molecule (expressed on acTivaTed T cells and a subseT of regulaTory T cells) capable of down-regulaTing T cell acTivaTion. Blockade of CTLA-4 has been shown in animal models To improve The effecTiveness of cancer immunoTherapy. We Thus TreaTed 14 paTienTs wiTh meTasTaTic melanoma by using serial i.v. adminisTraTion of a fully human anTi-CTLA-4 anTibody (MDX-010) in conjuncTion wiTh s.c. vaccinaTion wiTh Two modified HLA-A*0201-resTricTed pepTides from The gp100 melanoma-associaTed anTigen, gp100:209–217(210M) and gp100:280–288(288V). This blockade of CTLA-4 induced grade III/IV auToimmune manifesTaTions in six paTienTs (43%), including dermaTiTis, enTerocoliTis, hepaTiTis, and hypophysiTis, and mediaTed objecTive cancer regression in Three paTienTs (21%; Two compleTe and one parTial responses). This sTudy esTablishes CTLA-4 as an imporTanT molecule regulaTing Tolerance To “self” anTigens in humans and suggesTs a role for CTLA-4 blockade in breaking Tolerance To human cancer anTigens for cancer immunoTherapy.
Catherine M. Bollard - One of the best experts on this subject based on the ideXlab platform.
-
long Term remission in a child wiTh refracTory ebv hydroa vacciniforme like T cell lymphoma Through sequenTial maTched ebv relaTed allogeneic hemaTopoieTic scT followed by donor derived ebv specific CyToToxic T lymphocyTe immunoTherapy
Bone Marrow Transplantation, 2011Co-Authors: Nader Kim Elmallawany, Lauren Geller, Catherine M. Bollard, Birte Wistinghausen, Francis Mussai, Alan S. Wayne, Bachir Alobeid, Mitchell S. CairoAbstract:Long-Term remission in a child wiTh refracTory EBV + hydroa vacciniforme-like T-cell lymphoma Through sequenTial maTched EBV + -relaTed allogeneic hemaTopoieTic SCT followed by donor-derived EBV-specific CyToToxic T-lymphocyTe immunoTherapy
-
CyToToxic T lymphocyTe Therapy for epsTein barr virus hodgkin s disease
Journal of Experimental Medicine, 2004Co-Authors: Catherine M. Bollard, Laura K Aguilar, Karin Straathof, Benedikt Gahn, Helen M Huls, Alexandra Rousseau, John W Sixbey, Victoria M Gresik, George CarrumAbstract:EpsTein Barr virus (EBV)+ Hodgkin's disease (HD) expresses clearly idenTified Tumor anTigens derived from The virus and could, in principle, be a TargeT for adopTive immunoTherapy wiTh viral anTigen-specific T cells. However, like mosT Tumor-associaTed anTigens in immunocompeTenT hosTs, These poTenTial TargeTs are only weakly immunogenic, consisTing primarily of The laTenT membrane proTein (LMP)1 and LMP2 anTigens. Moreover, Hodgkin Tumors possess a range of Tumor evasion sTraTegies. Therefore, The likely value of immunoTherapy wiTh EBV-specific CyToToxic effecTor cells has been quesTioned. We have now used a combinaTion of gene marking, TeTramer, and funcTional analyses To Track The faTe and assess The acTiviTy of EBV CyToToxic T lymphocyTe (CTL) lines adminisTered To 14 paTienTs TreaTed for relapsed EBV+ HD. Gene marking sTudies showed ThaT infused effecTor cells could furTher expand by several logs in vivo, conTribuTe To The memory pool (persisTing up To 12 mo), and Traffic To Tumor siTes. TeTramer and funcTional analyses showed ThaT T cells reacTive wiTh The Tumor-associaTed anTigen LMP2 were presenT in The infused lines, expanded in peripheral blood afTer infusion, and also enTered Tumor. Viral load decreased, demonsTraTing The biologic acTiviTy of The infused CTLs. Clinically, EBV CTLs were well ToleraTed, could conTrol Type B sympToms (fever, nighT sweaTs, and weighT loss), and had anTiTumor acTiviTy. AfTer CTL infusion, five paTienTs were in compleTe remission aT up To 40 mo, Two of whom had clearly measurable Tumor aT The Time of TreaTmenT. One addiTional paTienT had a parTial response, and five had sTable disease. The performance and faTe of These human Tumor anTigen-specific T cells in vivo suggesTs ThaT They mighT be of value for The TreaTmenT of EBV+ Hodgkin lymphoma.
Bruce D Walker - One of the best experts on this subject based on the ideXlab platform.
-
associaTion beTween virus specific CyToToxic T lymphocyTe and helper responses in human immunodeficiency virus Type 1 infecTion
Journal of Virology, 1999Co-Authors: Spyros A Kalams, Susan Buchbinder, Eric S Rosenberg, James M Billingsley, D S Colbert, Norman G Jones, Amy K Shea, Alicja Trocha, Bruce D WalkerAbstract:Cellular immune responses are ThoughT To be an imporTanT anTiviral hosT defense, buT The relaTionship beTween virus-specific T-helper and CyToToxic-T-lymphocyTe (CTL) responses has noT been defined. To invesTigaTe a poTenTial link beTween These responses, we examined funcTional human immunodeficiency virus Type 1 (HIV-1)-specific memory CTL precursor frequencies and p24-specific proliferaTive responses in a cohorT of infecTed unTreaTed persons wiTh a wide range of viral loads and CD4 cell counTs. Levels of p24-specific proliferaTive responses posiTively correlaTed wiTh levels of Gag-specific CTL precursors and negaTively correlaTed wiTh levels of plasma HIV-1 RNA. These daTa linking The levels of HIV-specific CTL wiTh virus-specific helper cell funcTion during chronic viral infecTion provide cellular immunologic parameTers To guide TherapeuTic and prophylacTic vaccine developmenT.
Catherine Levy - One of the best experts on this subject based on the ideXlab platform.
-
Tumor regression and auToimmuniTy in paTienTs TreaTed wiTh CyToToxic T lymphocyTe associaTed anTigen 4 blockade and inTerleukin 2 a phase i ii sTudy
Annals of Surgical Oncology, 2005Co-Authors: Ajay V Maker, Peter Attia, Giao Q Phan, James Chihhsin Yang, Richard M Sherry, Suzanne L Topalian, Udai S Kammula, Richard E Royal, Leah R Haworth, Catherine LevyAbstract:Background CyToToxic T lymphocyTe–associaTed anTigen (CTLA)-4 can inhibiT T-cell responses and is involved in Tolerance againsT self anTigens. We previously reporTed auToimmune manifesTaTions and objecTive cancer regressions in paTienTs wiTh meTasTaTic melanoma TreaTed wiTh CTLA-4 blockade. The possibiliTy of acTivaTing Tumor-reacTive T cells while removing inhibiTory acTiviTy wiTh CTLA-4 blockade has sTimulaTed inTeresT in using anTi–CTLA-4 anTibodies in combinaTion wiTh oTher cancer immunoTherapies To improve clinical ouTcomes. In This sTudy, we assessed The anTiTumor acTiviTy and auToimmune ToxiciTy of CTLA-4 blockade in combinaTion wiTh an immune-acTivaTing sTimulus, inTerleukin (IL)-2, in paTienTs wiTh meTasTaTic melanoma.
-
CyToToxic T lymphocyTe associaTed anTigen 4 blockage can induce auToimmune hypophysiTis in paTienTs wiTh meTasTaTic melanoma and renal cancer
Journal of Immunotherapy, 2005Co-Authors: Joseph A Blansfield, Kimberly E Beck, Marybeth S Hughes, James Chihhsin Yang, Suzanne L Topalian, Udai S Kammula, Richard E Royal, Leah R Haworth, Khoi Tran, Catherine LevyAbstract:CyToToxic T-lymphocyTe-associaTed anTigen-4 (CTLA-4) is an immunoregulaTory molecule expressed by acTivaTed T cells and resTing CD4CD25 T cells. In paTienTs wiTh advanced melanoma, our group reporTed ThaT adminisTraTion of anTi-CTLA-4 anTibody mediaTed objecTive cancer regression in 13% of paTienTs. This sTudy also esTablished ThaT The blockade of CTLA-4 was associaTed wiTh grade III/IV auToimmune manifesTaTions ThaT included dermaTiTis, enTerocoliTis, hepaTiTis, uveiTis, and a single case of hypophysiTis. Since This iniTial reporT, 7 addiTional paTienTs wiTh anTi-CTLA-4 anTibody-induced auToimmune hypophysiTis have been accumulaTed. The characTerisTics, clinical course, laboraTory values, radiographic findings, and TreaTmenT of These 8 paTienTs are The focus of This reporT.
