TY - JOUR
T1 - Tumor antigen-specific induction of transcriptionally targeted retroviral vectors from chimeric immune receptor-modified T cells
AU - Chester, John
AU - Ruchatz, Anja
AU - Gough, Michael
AU - Crittenden, Marka
AU - Chong, Heung
AU - Loïc-Cosset, François
AU - Diaz, Rosa Maria
AU - Harrington, Kevin
AU - Alvarez-Vallina, Luis
AU - Vile, Richard
N1 - Funding Information:
Acknowledgments The authors thank Toni L. Higgins for expert secretarial assistance. This work was supported by the Mayo Foundation and by the Association of Cancer Physicians of the United Kingdom (J.C). We are grateful to Dr. Carlos Paya of the Mayo Clinic for supplying the (NF-κB)3 promoter fragment.
PY - 2002
Y1 - 2002
N2 - High-level systemic delivery of viral vectors to tumors has proved problematic as a result of immune neutralization, nonspecific adhesion, and clearance of circulating viral particles. Some cell types localize to tumors in response to particular biological properties associated with tumor growth. Their use to deliver viral vectors to tumors would allow precious viral stocks to be protected until they can be released at high local concentrations. Here, we describe a mechanism by which retroviral vector production by T cells can be regulated by a tumor-specific trigger through engagement of a chimeric immune receptor (CIR) with its target antigen. The virus that is released from the T cells can also be transcriptionally targeted. Finally, we show that it is possible to use vector-loaded, antigen-triggered human T cells as therapeutic, tumor-specific vector delivery cells in models of both local intratumoral and systemic delivery to both lung and liver metastases. This strategy incorporates multiple levels of targeting into the delivery system at the stages of surface targeting, viral production, and gene expression.
AB - High-level systemic delivery of viral vectors to tumors has proved problematic as a result of immune neutralization, nonspecific adhesion, and clearance of circulating viral particles. Some cell types localize to tumors in response to particular biological properties associated with tumor growth. Their use to deliver viral vectors to tumors would allow precious viral stocks to be protected until they can be released at high local concentrations. Here, we describe a mechanism by which retroviral vector production by T cells can be regulated by a tumor-specific trigger through engagement of a chimeric immune receptor (CIR) with its target antigen. The virus that is released from the T cells can also be transcriptionally targeted. Finally, we show that it is possible to use vector-loaded, antigen-triggered human T cells as therapeutic, tumor-specific vector delivery cells in models of both local intratumoral and systemic delivery to both lung and liver metastases. This strategy incorporates multiple levels of targeting into the delivery system at the stages of surface targeting, viral production, and gene expression.
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U2 - 10.1038/nbt0302-256
DO - 10.1038/nbt0302-256
M3 - Article
C2 - 11875426
AN - SCOPUS:0036200976
SN - 1087-0156
VL - 20
SP - 256
EP - 263
JO - Nature biotechnology
JF - Nature biotechnology
IS - 3
ER -