The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies

Traversari, Catia; Marktel, Sarah; Magnani, Zulma; Mangia, Patrizia; Russo, Vincenzo; Ciceri, Fabio; Bonini, Chiara; Bordignon, Claudio

doi:10.1182/blood-2006-04-015230

Cited by 184 publications

(146 citation statements)

References 31 publications

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“…Therefore, HSV-tk-modified T cells can be selectively killed by administering GCV to the patients. 8,9 However, in a clinical study 7 out the 23 patients treated developed a strong cytolytic T-lymphocytes (CTL) immune response against the HSV-tk protein, 10 even though, in this particular example the immune response did not affect the efficacy of the therapy.…”

Section: Responses Against the Transgene Productmentioning

confidence: 99%

How not to be seen: immune-evasion strategies in gene therapy

Zaldumbide

Hoeben

2007

Gene Ther

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Section: Responses Against the Transgene Productmentioning

confidence: 99%

How not to be seen: immune-evasion strategies in gene therapy

Zaldumbide

Hoeben

2007

Gene Ther

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“…This strategy may find a place in preventing relapse, selectively controlling GVHD and/or enhancing wide-spectrum immunological reconstitution after transplantation. 70 Results of ex vivo-expanded immunomodulatory cells (T-regs, NK/T-regs, MSCs and donor-derived NK), [71][72][73][74] adoptive transfer of allogeneic T cells that are specific for viral 65,67,[75][76][77][78] or tumour antigens 79 appear promising. All these diverse approaches show that cell therapy is feasible after haploidentical transplantation and may help re-build immunity to infections.…”

Section: Trm and Post Transplant Immune Re-buildingmentioning

confidence: 99%

Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States

Aversa

2008

Bone Marrow Transplant

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Work on one haplotype-mismatched transplants has been proceeding for over 20 years all over the world and novel transplant techniques have been developed. Some centres have focused on the conditioning regimens and post transplant immune suppression; others have concentrated on manipulating the graft. Haploidentical transplant modalities are based mainly on high-intensity conditioning regimen, but reduced intensity regimens have recently been introduced. The graft may be a megadose of extensively T cell-depleted or unmanipulated progenitor cells. Excellent engraftment rates are associated with a very low incidence of GVHD-and regimen-related mortality even in patients who are over 50 years old. Overall, event-free survival and transplant-related mortality compare favourably with reports on transplants from sources of stem cells other than the matched sibling. Improvements will come with successful implementation of strategies to accelerate and strengthen post transplant immune reconstitution as well as transplantation of patients in early stage disease.

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“…123 Finally, given the potential for gene transfer to cause unwanted genotoxicity, investigators have included suicide genes [124][125][126][127][128][129][130][131][132] which conditionally render the cells sensitive to ablation in the event of an adverse event such as GVHD. [133][134][135][136] Adoptive cellular immunotherapy in the future There are a number of challenges to broadening the application of adoptive cellular immunotherapy for childhood cancers. The therapeutic effect of infused tumorspecific T cells for pediatric malignancies will depend on the persistence of the adoptively transferred cells, their ability to home, and their ability to operate and repetitively kill within the tumor microenvironment.…”

Section: Adoptive Cellular Immunotherapy Using Genetically Modified Tmentioning

confidence: 99%

Adoptive cellular immunotherapy for childhood malignancies

Cooper

2007

Bone Marrow Transplant

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Clinical trials have established that T cells have the ability to prevent and treat pathogens and tumors. This is perhaps best exemplified by engraftment of allogeneic T cells in the context of hematopoietic stem-cell transplantation (HSCT), which for over the last 50 years remains one of the best and most robust examples of cell-based therapies for the treatment of hematologic malignancies. Yet, the approach to infuse T cells for treatment of cancer, in general, and pediatric tumors, in particular, generally remains on the sidelines of cancer therapy. This review outlines the current state-of-the-art and provides a rationale for undertaking adoptive immunotherapy trials with emphasis on childhood malignancies.

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The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies

Cited by 184 publications

References 31 publications

How not to be seen: immune-evasion strategies in gene therapy

How not to be seen: immune-evasion strategies in gene therapy

Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States

Adoptive cellular immunotherapy for childhood malignancies

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