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T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer.
Gene Ther. 2002 Jun; 9(12):786-92.GT

Abstract

We have shown that interleukin-12 (IL-12) generated a strong, albeit transient, anti-tumor response, mostly mediated by natural killer (NK) cell. T cell participation, in addition to NK cells, was essential for persistence of the anti-tumor response. Ligation of 4-1BB, a co-stimulatory receptor expressed on activated T cells, is known to amplify T cell-mediated immunity. In this study, we compared the effect of a systemically delivered agonistic anti-4-1BB monoclonal antibody (anti-4-1BB mAb) with intra-tumoral adenoviral-mediated gene transfer of the 4-1BB ligand (ADV/4-1BBL) to liver metastases in a syngeneic animal model of breast cancer. Both treatments induced a dramatic regression of pre-established tumor. When combined with intra-tumoral delivery of the IL-12 gene, both anti-4-1BB mAb and ADV/4-1BBL were synergistic and led to survival rates of 87% and 78%, respectively. The anti-tumor immunity is mainly mediated by CD4+ T cells in IL-12 plus 4-1BB ligand-treated animals, and CD8+ T cells in IL-12 plus anti-4-1BB mAb-treated animals. However, only long-term survivors after treatment with IL-12 and 4-1BBL genes have showed significantly potent, systemic, and tumor-specific T cell-mediated immunity.

Authors+Show Affiliations

Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12040460

Citation

Martinet, O, et al. "T Cell Activation With Systemic Agonistic Antibody Versus Local 4-1BB Ligand Gene Delivery Combined With Interleukin-12 Eradicate Liver Metastases of Breast Cancer." Gene Therapy, vol. 9, no. 12, 2002, pp. 786-92.
Martinet O, Divino CM, Zang Y, et al. T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer. Gene Ther. 2002;9(12):786-92.
Martinet, O., Divino, C. M., Zang, Y., Gan, Y., Mandeli, J., Thung, S., Pan, P. Y., & Chen, S. H. (2002). T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer. Gene Therapy, 9(12), 786-92.
Martinet O, et al. T Cell Activation With Systemic Agonistic Antibody Versus Local 4-1BB Ligand Gene Delivery Combined With Interleukin-12 Eradicate Liver Metastases of Breast Cancer. Gene Ther. 2002;9(12):786-92. PubMed PMID: 12040460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer. AU - Martinet,O, AU - Divino,C M, AU - Zang,Y, AU - Gan,Y, AU - Mandeli,J, AU - Thung,S, AU - Pan,P-Y, AU - Chen,S-H, PY - 2001/06/28/received PY - 2002/01/14/accepted PY - 2002/6/1/pubmed PY - 2002/8/10/medline PY - 2002/6/1/entrez SP - 786 EP - 92 JF - Gene therapy JO - Gene Ther VL - 9 IS - 12 N2 - We have shown that interleukin-12 (IL-12) generated a strong, albeit transient, anti-tumor response, mostly mediated by natural killer (NK) cell. T cell participation, in addition to NK cells, was essential for persistence of the anti-tumor response. Ligation of 4-1BB, a co-stimulatory receptor expressed on activated T cells, is known to amplify T cell-mediated immunity. In this study, we compared the effect of a systemically delivered agonistic anti-4-1BB monoclonal antibody (anti-4-1BB mAb) with intra-tumoral adenoviral-mediated gene transfer of the 4-1BB ligand (ADV/4-1BBL) to liver metastases in a syngeneic animal model of breast cancer. Both treatments induced a dramatic regression of pre-established tumor. When combined with intra-tumoral delivery of the IL-12 gene, both anti-4-1BB mAb and ADV/4-1BBL were synergistic and led to survival rates of 87% and 78%, respectively. The anti-tumor immunity is mainly mediated by CD4+ T cells in IL-12 plus 4-1BB ligand-treated animals, and CD8+ T cells in IL-12 plus anti-4-1BB mAb-treated animals. However, only long-term survivors after treatment with IL-12 and 4-1BBL genes have showed significantly potent, systemic, and tumor-specific T cell-mediated immunity. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/12040460/T_cell_activation_with_systemic_agonistic_antibody_versus_local_4_1BB_ligand_gene_delivery_combined_with_interleukin_12_eradicate_liver_metastases_of_breast_cancer_ L2 - https://doi.org/10.1038/sj.gt.3301687 DB - PRIME DP - Unbound Medicine ER -