Genetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regression

作者：Li, S; Yang, J; Urban, F A; MacGregor, J N; Hughes, D P M; Chang, A E; Mcdonagh, K T; Li, Q^*

来源：Cancer Gene Therapy, 2008, 15(6): 382-392.

DOI：10.1038/cgt.2008.5

• adoptive immunotherapy
• HER2
• chimeric receptor
• breast cancer
• fibrosarcoma
• IL-2

In this report, we developed a chimeric receptor ( N29 gamma chR) involving the single chain Fv ( scFv) derived from N29 monoclonal antibody ( mAb) specific for p185HER2 and characterized the therapeutic efficacy of primary T cells engineered to express N29g chR in two histologically distinct murine tumor models. Murine breast ( MT901) and fibrosarcoma ( MCA207) cancer cell lines were engineered to express human HER2 as targets. Administration of N29 gamma chR-expressing T cells eliminated 3-day pulmonary micrometastases of MT901/ HER2 and MCA207/ HER2 but not parental tumor cells. A 5 to 8-fold increased dose of N29g T cells was required to mediate regression of advanced 8-day macrometastases. Exogenous administration of interleukin-2 ( IL-2) after N29g T-cell transfer was dispensable for treatment of 3-day micrometastases, but was required for mediating regression of well-established 8-day macrometastases. Moreover, fractionated CD8 T cells expressing N29g chR suppressed HER2-positive tumor cell growth after adoptive transfer independent of CD4( ) cells. These data indicate that genetically modified T cells expressing a HER2-targeting chimeric receptor can mediate antigen-specific regression of preestablished metastatic cancers in a cell dose-dependent fashion. Systemic administration of IL-2 augments the therapeutic efficacy of these genetically engineered T cells in advanced diseases. These results are relevant to the implication of genetically redirected T cells in clinical cancer immunotherapy.

• 出版日期2008-6
• 单位中山大学; 中国人民解放军第二军医大学