Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells

Liu, Yong; Chiriva‐Internati, Maurizio; You, Changxuan; Luo, Rong; You, Hong; Prasad, C. Krishna; Grizzi, Fabio; Cobos, Everardo; Klimberg, V. Suzanne; Kay, Helen H.; Mehta, Jawahar L.; Hermonat, Paul L.

doi:10.1038/sj.cgt.7700785

Cited by 21 publications

(10 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the L form containing a Pro/Thr-enriched domain facilitates phagocytosis of apoptotic cells by macrophages (Hanayama et al, 2002(Hanayama et al, , 2004, the S form was reported to support the gamete interaction upon fertilization (Ensslin and Shur, 2003). Very importantly, recent studies determined peptide sequences derived from human MFG-E8 as the potential targets for tumor immunotherapy (Carmon et al, 2002;Liu et al, 2005).…”

mentioning

confidence: 99%

p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and ΔN isoforms

et al. 2007

View full text Add to dashboard Cite

We report here that human MFGE8 encoding milk fat globule-EGF factor 8 protein (MFG-E8), also termed 46 kDa breast epithelial antigen and lactadherin, is transcriptionally activated by p63, or TP63, a p53 (TP53) family protein frequently overexpressed in head-and-neck squamous cell carcinomas, mammary carcinomas and so on. Despite that human MFG-E8 was originally identified as a breast cancer marker, and has recently been reported to provide peptides for cancer immunotherapy, its transcriptional control remains an open question. Observations in immunohistochemical analyses, a tetracycline-induced p63 expression system and keratinocyte cultures suggested a physiological link between p63 and MFGE8. By reporter assays with immediately upstream regions of MFGE8, we determined that the trans-activator (TA) isoforms of p63 activate MFGE8 transcription though a p53/p63 motif at À370, which was confirmed by a chromatin immunoprecipitation experiment. Upon siRNAmediated p63 silencing in a squamous cell carinoma line, MFG-E8 production decreased to diminish Saos-2 cell adhesion. Interestingly, the DN-p63 isoform lacking the TA domain enhanced the MFGE8-activating function of TA-p63, if DN-p63 was dominant over TA-p63 as typically observed in undifferentiated keratinocytes and squamous cell carcinomas, implying a self-regulatory mechanism of p63 by the TA:DN association. MFG-E8 may provide a novel pathway of epithelial-nonepithelial cell interactions inducible by p63, probably in pathological processes.

show abstract

mentioning

confidence: 99%

p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and ΔN isoforms

et al. 2007

View full text Add to dashboard Cite

show abstract

“…AAV1 [Veron et al, 2007], AAV2 [Liu et al, 2005;Ponnazhagan et al, 2001;Veron et al, 2007] and AAV6 [Aldrich et al, 2006] have been shown to transduce DC cultures ex vivo in studies aimed at achieving adaptive immunity to the vector encoded product (Fig. 1ab).…”

Section: Transgene Product Specific Immune Responsesmentioning

confidence: 96%

AAV as An Immunogen

Vandenberghe

Wilson²

2007

CGT

View full text Add to dashboard Cite

The first in vivo adeno-associated viral vector (AAV) gene transfer experiments were performed in murine models of muscle directed gene transfer. These studies were remarkable for stable expression of a variety of immunogenic transgenes. These findings were translated to other target organs with multiple therapeutic gene products. Technological improvements and the lessons learned from basic research have heralded an era of first-in-human clinical trials. In most settings, AAV appears to evade host immune surveillance, allowing the delivery of robust levels of genetic cargo that leads to persistent expression. However, in few experimental settings immunological responses raised following AAV mediated gene transfer have compromised vector efficacy. Parameters that determine these occurrences have been proposed to be pre-existing immunity to AAV, the route of administration, the kinetics of expression, the dose, the vector serotype and its ability to transduce antigen-presenting cells (APCs) as well as the host species and nature of the specific transgene product. Overall, the underlying mechanisms remain the topic of scientific debate. This review aims to compile, confront and critically discuss the findings in which AAV appears to be an immunogen.

show abstract

“…Since the immunotherapy has offered great promises for treatment of cancers, many approaches have been exploited to use AAV vectors to deliver genes to stimulate the immune response against tumors (39)(40)(41)(42)(43)(44)(45)(46)(47). Mohr et al demonstrated that the tumor growth in the mice transduced with an AAV2/TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) vector was greatly suppressed (41).…”

Section: Immunotherapymentioning

confidence: 99%

Cancer gene therapy using adeno-associated virus vectors

Park¹

2008

Front Biosci

View full text Add to dashboard Cite

Gene therapy has offered highly possible promises for treatment of cancers, as many potential therapeutic genes involved in regulation of molecular processes may be introduced by gene transfer, which can arrest angiogenesis, tumor growth, invasion, metastasis, and/or can stimulate the immune response against tumors. Therefore, viral and non-viral gene delivery systems have been developed to establish an ideal delivery vector for cancer gene therapy over the past several years. Among the currently developed virus vectors, the adeno-associated virus (AAV) vector is considered as one of those that are closest to the ideal vector mainly for genetic diseases due to the following prominent features; the lack of pathogenicity and toxicity, ability to infect dividing and non-dividing cells of various tissue origins, a very low host immune response and long-term expression. Particularly, the most important attribute of AAV vectors is their safety profile in clinical trials ranging from CF to Parkinson's disease. Although adenovirus and several other oncolytic viruses have been more frequently used to develop cancer gene therapy, AAV also has many critical properties to be exploited for a cancer gene delivery vector. In this review, we will briefly summarize the basic biology of AAV and then mainly focus on recent progresses on AAV vector development and AAV-mediated therapeutic vectors for cancer gene therapy.

show abstract

Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells

Cited by 21 publications

References 33 publications

p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and ΔN isoforms

p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and ΔN isoforms

AAV as An Immunogen

Cancer gene therapy using adeno-associated virus vectors

Contact Info

Product

Resources

About