Over the last two decades,lymphoma idiotype vaccines have been the first human cancer vaccines to show striking evidence of biological and clinical efficacy on the one hand,as well as clinical benefit on the other.Mor...Over the last two decades,lymphoma idiotype vaccines have been the first human cancer vaccines to show striking evidence of biological and clinical efficacy on the one hand,as well as clinical benefit on the other.More recently,however,three large-scale,independent,randomized clinical trials on idiotypic vaccination have failed to achieve their main clinical endpoints for reasons likely to depend more on flaws in each clinical trial’s study design than on each vaccination strategy per se.Independently of these considerations,a major hurdle for the development of this substantially innocuous and yet potentially very effective type of treatment has been the fact that,even to date,no factors ascertainable before vaccination have been prospectively singled out as predictors of subsequently vaccine-induced,idiotypespecific immune as well as clinical responses.The aim of this review article is precisely to analyze what has been and what could be done in this respect in order to give a greater chance of success to future trials aimed at regulatory approval of idiotype vaccines.展开更多
Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth sense.The perception of...Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth sense.The perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological systems.In addition to the direct effects of sense-induced mediators in the brain.展开更多
AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurabl...AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurable glioblastoma multiform. METHODS: Preliminary to our ongoing, phase-Ⅱ clinical trial, we conducted a small pilot study enrolling five consecutive patients with resectable glioblastoma. In terms of Recursive Partitioning Analysis, four patientswere class Ⅴ and one was class Ⅳ. In all five cases, fluorescence-guided surgery was employed, followed by rapid steroid discontinuation. Patients were then treated with a combination of standard radio-chemotherapy with temozolomide and tumor lysate-pulsed, mature dendritic cell-based vaccinations.RESULTS: Though all five patients ultimately progressed, with any further treatment left to the sole decision of the treating oncologist, active immunotherapy was very well tolerated and induced specific immune responses in all three patients for whom enough material was available for such an assessment. Median progression-free survival was 16.1 mo. Even more important, median and mean overall survival were 27 mo and 26 mo, respectively. Three patients have died with an overall survival of 9 mo, 27 mo and 27.4 mo, while the other two are still alive at 32 mo and 36 mo, the former receiving treatment with bevacizumab, while the latter has now been off therapy for 12 mo. Four of five patients were alive at two years.CONCLUSION: Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-Ⅱ study is ongoing to possibly improve further on our very encouraging clinical results.展开更多
Cord blood(CB)plays an important role as a medical resource containing hematopoietic stem cells(HSCs)and mature immune cells.Cord blood transplantation(CBT)for hematopoietic disorders offers several advantages,includi...Cord blood(CB)plays an important role as a medical resource containing hematopoietic stem cells(HSCs)and mature immune cells.Cord blood transplantation(CBT)for hematopoietic disorders offers several advantages,including the ability to initiate treatment early,lower rates of severe chronic graft-versus-host disease even in human leukocyte antigen(HLA)-mismatched recipients,resulting in better post-transplant quality of life,and stronger anti-tumor immune responses compared to other transplantation methods,thereby reducing the risk of post-transplant relapse. In addition,techniques such as the introduction of chimeric antigen receptor genes have been used to enable immune cells in CB,such as T cells and natural killer(NK)cells,to be used as sources for cell therapies.展开更多
文摘Over the last two decades,lymphoma idiotype vaccines have been the first human cancer vaccines to show striking evidence of biological and clinical efficacy on the one hand,as well as clinical benefit on the other.More recently,however,three large-scale,independent,randomized clinical trials on idiotypic vaccination have failed to achieve their main clinical endpoints for reasons likely to depend more on flaws in each clinical trial’s study design than on each vaccination strategy per se.Independently of these considerations,a major hurdle for the development of this substantially innocuous and yet potentially very effective type of treatment has been the fact that,even to date,no factors ascertainable before vaccination have been prospectively singled out as predictors of subsequently vaccine-induced,idiotypespecific immune as well as clinical responses.The aim of this review article is precisely to analyze what has been and what could be done in this respect in order to give a greater chance of success to future trials aimed at regulatory approval of idiotype vaccines.
基金supported by a grant from the Department of Economic and Business Development from the Government of Navarra(INNOLFACT project,Ref.0011-1411-2023-000094)。
文摘Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth sense.The perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological systems.In addition to the direct effects of sense-induced mediators in the brain.
基金Supported by Spanish Health Ministry Grant MCI EC08/00186
文摘AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurable glioblastoma multiform. METHODS: Preliminary to our ongoing, phase-Ⅱ clinical trial, we conducted a small pilot study enrolling five consecutive patients with resectable glioblastoma. In terms of Recursive Partitioning Analysis, four patientswere class Ⅴ and one was class Ⅳ. In all five cases, fluorescence-guided surgery was employed, followed by rapid steroid discontinuation. Patients were then treated with a combination of standard radio-chemotherapy with temozolomide and tumor lysate-pulsed, mature dendritic cell-based vaccinations.RESULTS: Though all five patients ultimately progressed, with any further treatment left to the sole decision of the treating oncologist, active immunotherapy was very well tolerated and induced specific immune responses in all three patients for whom enough material was available for such an assessment. Median progression-free survival was 16.1 mo. Even more important, median and mean overall survival were 27 mo and 26 mo, respectively. Three patients have died with an overall survival of 9 mo, 27 mo and 27.4 mo, while the other two are still alive at 32 mo and 36 mo, the former receiving treatment with bevacizumab, while the latter has now been off therapy for 12 mo. Four of five patients were alive at two years.CONCLUSION: Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-Ⅱ study is ongoing to possibly improve further on our very encouraging clinical results.
文摘Cord blood(CB)plays an important role as a medical resource containing hematopoietic stem cells(HSCs)and mature immune cells.Cord blood transplantation(CBT)for hematopoietic disorders offers several advantages,including the ability to initiate treatment early,lower rates of severe chronic graft-versus-host disease even in human leukocyte antigen(HLA)-mismatched recipients,resulting in better post-transplant quality of life,and stronger anti-tumor immune responses compared to other transplantation methods,thereby reducing the risk of post-transplant relapse. In addition,techniques such as the introduction of chimeric antigen receptor genes have been used to enable immune cells in CB,such as T cells and natural killer(NK)cells,to be used as sources for cell therapies.
