PMID- 20559334 OWN - NLM STAT- MEDLINE DCOM- 20101214 LR - 20141120 IS - 1476-5500 (Electronic) IS - 0929-1903 (Linking) VI - 17 IP - 10 DP - 2010 Oct TI - Direct and indirect antitumor effects by human peripheral blood lymphocytes expressing both chimeric immune receptor and interleukin-2 in ovarian cancer xenograft model. PG - 742-50 LID - 10.1038/cgt.2010.30 [doi] AB - Human peripheral blood lymphocytes (PBLs) electroporated with RNA encoding anti-Her-2/neu-specific chimeric immune receptor (CIR) have been reported to elicit potent immune responses against SKOV3 tumors in a nude mouse model. However, CIR-electroporated PBL (CIR-PBL) did not proliferate, and the cell number rapidly decreased in the absence of exogenous interleukin-2 (IL-2). In this study, PBLs electroporated with both CIR and IL-2 RNA (CIR/IL-2-PBL) were studied to determine whether antitumor effects could be improved by adoptive immunotherapy. CIR and IL-2 were expressed in CIR/IL-2-PBL at levels similar to PBLs electroporated, with IL-2 RNA (IL-2-PBL) or CIR-PBL. Transfer of IL-2 RNA induced proliferation and prolonged survival of PBLs in vitro. In a xenograft model, both IL-2-PBL and CIR/IL-2-PBL showed significantly higher antitumor effects than CIR-PBL. The number of tumor-infiltrating natural killer (NK) cells was significantly increased in IL-2-PBL and CIR/IL-2-PBL. After NK cell depletion, IL-2-PBL showed significantly lower antitumor effects than CIR/IL-2-PBL. These results suggest that transfer of IL-2 RNA to CIR-PBL can promote NK cell infiltration of tumors and prolong survival of infused PBLs in vivo. RNA electroporated PBLs may represent efficient tools for delivery of functional molecules to tumors by multiple gene transfer. FAU - Lee, J M AU - Lee JM AD - Department of Microbiology, College of Medicine, The Catholic University of Korea, Seocho-Gu, Seoul, Republic of Korea. FAU - Yoon, S H AU - Yoon SH FAU - Kim, H-S AU - Kim HS FAU - Kim, S Y AU - Kim SY FAU - Sohn, H-J AU - Sohn HJ FAU - Oh, S-T AU - Oh ST FAU - Oh, I-H AU - Oh IH FAU - Kim, T-G AU - Kim TG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100618 PL - England TA - Cancer Gene Ther JT - Cancer gene therapy JID - 9432230 RN - 0 (Antineoplastic Agents) RN - 0 (Interleukin-2) RN - 0 (Receptors, Natural Killer Cell) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Animals MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma/immunology/therapy MH - Disease Models, Animal MH - Electroporation MH - Female MH - Humans MH - *Immunotherapy, Adoptive MH - Interleukin-2/*pharmacology MH - Killer Cells, Natural/drug effects/immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Ovarian Neoplasms/immunology/*therapy MH - Receptor, ErbB-2/immunology MH - Receptors, Natural Killer Cell/immunology/therapeutic use MH - Tumor Cells, Cultured MH - *Xenograft Model Antitumor Assays EDAT- 2010/06/19 06:00 MHDA- 2010/12/16 06:00 CRDT- 2010/06/19 06:00 PHST- 2010/06/19 06:00 [entrez] PHST- 2010/06/19 06:00 [pubmed] PHST- 2010/12/16 06:00 [medline] AID - cgt201030 [pii] AID - 10.1038/cgt.2010.30 [doi] PST - ppublish SO - Cancer Gene Ther. 2010 Oct;17(10):742-50. doi: 10.1038/cgt.2010.30. Epub 2010 Jun 18.