Adaptive and innate immune responses to gene transfer vectors: role of cytokines and chemokines in vector function

Characterisation of systemic dissemination of nonreplicating adenoviral vectors from tumours in local gene delivery

“…The most widely used vectors for gene delivery are genetically engineered viruses, because they, in the long-term evolution of nature, are equipped with specific machineries that facilitate DNA transport into the nucleus of cells (Baranowski et al, 2001). However, a main drawback of viral vectors is the toxicity caused by undesirable acute immune response to viral proteins (Brown and Lillicrap, 2002;Bowers et al, 2003;Chen et al, 2003;Jooss and Chirmule, 2003;Lowenstein, 2003). Moreover, proteins from transgene expression may also exert adverse effects on normal cells either directly or indirectly through conversion of prodrugs to cytotoxic agents (Freeman et al, 1993;Rosenfeld et al, 1995;Alvarez and Curiel, 1997;Pope et al, 1997;Chada et al, 2003).…”

Evolving gene therapy approaches for osteosarcoma using viral vectors: Review

“…In addition, the cellular immune response, mediated through adenoviral specific CD8 positive T cells, eliminate the cells' expressing viral and transgene products (24). Overall the undesirable acute immune response to viral proteins was considered the main drawback of virus-based gene therapy (13,14,16).…”

Virology and immunology of gene therapy, or virology and immunology of high MOI infection with defective viruses

“…Especially, this issue surveys the inflammatory and immune responses to HSV-1 vectors, 5 AAV-vectors, 9,10 adenovirus vectors, 6,9,11 and further investigates how different arms of the immune response affect both replication-defective 5,6,9 and replication-competent vectors. 5,12,13 Of further importance to the field, this issue explores how inflammatory and immune responses will vary, even for the same vector, depending on the target organ being injected and transduced. 6,11,13 Thus, this special issue examines immune responses to vectors infecting different tissues, that is, muscle, 9 liver, 10 eye, 11 and brain.…”

“…5,12,13 Of further importance to the field, this issue explores how inflammatory and immune responses will vary, even for the same vector, depending on the target organ being injected and transduced. 6,11,13 Thus, this special issue examines immune responses to vectors infecting different tissues, that is, muscle, 9 liver, 10 eye, 11 and brain. 6 Main themes of this issue include early inflammatory responses and signaling pathways activated by viral vectors; 4 how viral vectors stimulate the release of inflammatory mediators, cytokines, and 9 the mechanisms by which the innate and/or adaptive arm of the immune response can inhibit transgene expression (or eliminate transduced cells).…”

“…6 Main themes of this issue include early inflammatory responses and signaling pathways activated by viral vectors; 4 how viral vectors stimulate the release of inflammatory mediators, cytokines, and 9 the mechanisms by which the innate and/or adaptive arm of the immune response can inhibit transgene expression (or eliminate transduced cells). 6,12,13 Clinical immune responses have not been discussed, since they were reviewed (at least those concerning adenoviral vectors) in detail elsewhere. 14 While the astute reader will find no quick answers on how to 'get away with it', that is, forgetting the immune response continues to impose a major theoretical and practical hurdle to the safe implementation of clinical gene therapy, the goal is to share with the larger gene therapy community, the possibility that by understanding the molecular and cellular mechanisms underlying the activation of immune responses by viral vectors, and the elucidation of the pathways by which activated arms of the inflammatory and immune pathways interact with transduced cells, the field will be on the high ground to design better and safer vectors, and implement more effective and compelling clinical trials.…”