TY - JOUR T1 - In Vivo Evaluation of a Cancer Therapy Strategy Combining HSV1716-Mediated Oncolysis with Gene Transfer and Targeted Radiotherapy JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 647 LP - 654 DO - 10.2967/jnumed.111.090886 VL - 53 IS - 4 AU - Annette Sorensen AU - Robert J. Mairs AU - Lynne Braidwood AU - Craig Joyce AU - Joe Conner AU - Sally Pimlott AU - Moira Brown AU - Marie Boyd Y1 - 2012/04/01 UR - http://jnm.snmjournals.org/content/53/4/647.abstract N2 - Oncolytic herpes viruses show promise for cancer treatment. However, it is unlikely that they will fulfill their therapeutic potential when used as monotherapies. An alternative strategy is to use these viruses not only as oncolytic agents but also as a delivery mechanism of therapeutic transgenes to enhance tumor cell killing. The herpes simplex virus 1 deletion mutant HSV1716 is a conditionally replicating oncolytic virus that selectively replicates in and lyses dividing tumor cells. It has a proven safety profile in clinical trials and has demonstrated efficacy as a gene-delivery vehicle. To enhance its therapeutic potential, we have engineered HSV1716 to convey the noradrenaline transporter (NAT) gene (HSV1716/NAT), whose expression endows infected cells with the capacity to accumulate the noradrenaline analog metaiodobenzylguanidine (MIBG). Thus, the NAT gene–infected cells are susceptible to targeted radiotherapy using radiolabeled 131I-MIBG, a strategy that has already shown promise for combined targeted radiotherapy–gene therapy in cancer cells after plasmid-mediated transfection. Methods: We used HSV1716/NAT as a dual cell lysis–gene delivery vehicle for targeting the NAT transgene to human tumor xenografts in vivo. Results: In tumor xenografts that did not express NAT, intratumoral or intravenous injection of HSV1716/NAT induced the capacity for active uptake of 131I-MIBG. Administration of HSV1716/NAT and 131I-MIBG resulted in decreased tumor growth and enhanced survival relative to injection of either agent alone. Efficacy was dependent on the scheduling of delivery of the 2 agents. Conclusion: These findings support a role for combination radiotherapy–gene therapy for cancer using HSV1716 expressing the NAT transgene and targeted radionuclide therapy. ER -