Interactions between the Immune System and Gene Therapy Vectors: Bidirectional Regulation of Response and Expression**Received for publication September 19, 1997

1998 ◽  
pp. 353-409 ◽  
Author(s):  
Jonathan S. Bromberg ◽  
Lisa A. Debruyne ◽  
Lihui Qin
Author(s):  
Carsten Brunn ◽  
Takashi Kei Kishimoto

In recent months as vaccines against the SARS-CoV-2 virus continue to rollout across the globe, there has been a renewed interest in ways to activate or ignite the immune system. For a vaccine to be effective, it must be immunogenic and specific to provoke the body's defenses to mount an effective response that protects the host from disease. However, there are other situations wherein the immune system mounts an unwanted immune response that can be detrimental to health, either directly, by causing an autoimmune disease, or indirectly, by compromising the safety and/or efficacy of biologic drugs. In these scenarios, it would be desirable to have a ‘tolerogenic vaccine’ that could selectively and effectively mitigate these unwanted immune responses. ImmTORTM, a nanoparticle technology, is being developed to address the issue of immunogenicity for gene therapy vectors and other biologic drugs. By targeting antigen-presenting cells, ImmTORTM has the potential to amplify the efficacy of biologic therapies and unlock the full potential of such treatments to improve the lives of those who suffer from serious and debilitating diseases.


Author(s):  
Jared S. Bee ◽  
Kristin O'Berry ◽  
Yu (Zoe) Zhang ◽  
Megan Kuhn Phillippi ◽  
Akanksha Kaushal ◽  
...  

2005 ◽  
Vol 90 (4) ◽  
pp. 391-404 ◽  
Author(s):  
Mar�a de las Mercedes Segura ◽  
Amine Kamen ◽  
Pierre Trudel ◽  
Alain Garnier

2010 ◽  
Vol 18 (8) ◽  
pp. 1422-1429 ◽  
Author(s):  
Dmitry M Shayakhmetov ◽  
Nelson C Di Paolo ◽  
Karen L Mossman

Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2071-2076 ◽  
Author(s):  
José L. Cohen ◽  
Olivier Boyer ◽  
David Klatzmann

After allogeneic hematopoietic stem cell transplantation (HSCT), mature transplanted T cells play a major role in restoration of the immune system. However, they can also induce a life-threatening complication: graft-versus-host disease (GVHD). Suicide gene therapy of GVHD aims to selectively eliminate alloreactive T cells mediating GVHD while sparing nonalloreactive T cells that should contribute to immune reconstitution. It was demonstrated previously that treatment with ganciclovir (GCV) can control GVHD in mice by killing donor T cells engineered to express the thymidine kinase (TK) suicide gene. TK allows phosphorylation of nontoxic GCV into triphosphate GCV, which is selectively toxic for dividing cells. Thus, in the TK-GCV system, the specificity of cell killing depends on the cycling status of TK T cells rather than allogeneic recognition. This is a potential drawback because in recipients of lymphopenic allogeneic HSCT, alloreactive and homeostatic signals drive the proliferation of donor T cells. It is shown here that the onset of alloreactive T-cell division occurs earlier than that of nonalloreactive T cells, thus establishing a time frame for GCV administration. A 7-day GCV treatment initiated at the time of HSCT allowed efficient prevention of GVHD, while sparing a pool of nondividing donor TK T cells. These cells later expanded and contributed to the replenishment of the recipient immune system with a diversified T-cell receptor repertoire. These results provide a rationale for designing the therapeutic scheme when using TK-GCV suicide gene therapy in allogeneic HSCT.


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