Dendritic Cells Retrovirally Transduced with a Model Antigen Gene Are Therapeutically Effective against Established Pulmonary Metastases

• DOI: 10.1084/jem.186.8.1213
• Publication Date: 2002-07-26T16:48:54Z
• Authors: Jennifer M. Specht; Gang Wang; My T. Do; John S. Lam; Richard E. Royal; Mark E. Reeves; Steven A. Rosenberg; Patrick Hwu
• Keywords: Antigen Presentation; Mice, Inbred BALB C; Lung Neoplasms; Carcinoma; Gene Transfer Techniques; Models, Immunological; Bone Marrow Cells; Cell Differentiation; Dendritic Cells; Lymphocyte Activation; beta-Galactosidase; Immunotherapy, Adoptive; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Colonic Neoplasms; Tumor Cells, Cultured; Animals; Female; Lymphocyte Culture Test, Mixed; Moloney murine leukemia virus; T-Lymphocytes, Cytotoxic

Dendritic cells (DCs) are bone marrow-derived leukocytes that function as potent antigen presenting capable of initiating T cell-dependent responses from quiescent lymphocytes. DC pulsed with tumor-associated (TAA) peptide or protein have recently been demonstrated to elicit antigen-specific protective antitumor immunity in a number murine models. Transduction DCs TAA genes may allow stable, prolonged expression well the potential for presentation multiple, unidentified, epitopes association major histocompatibility complex class I and/or II molecules. To evaluate efficacy retrovirally transduced DCs, marrow harvested BALB/c mice were either model gene encoding beta-galactosidase (beta-gal) control rat HER-2/neu (Neu) by coculture irradiated ecotropic retroviral producer lines. Bone differentiated into vitro using granulocyte/macrophage colony-stimulating factor and interleukin-4. After 7 d culture, 45-78% double positive phenotypic cell surface markers FACS(R) analysis, beta-gal 41-72% X-gal staining. In addition, beta-gal-specific line (CTLx) resulted production large amounts interferon-gamma, demonstrating could process present endogenously expressed beta-gal. then used treat 3-d lung metastases bearing an experimental tumor CT26.CL25, expressing antigen, Treatment beta-gal-transduced significantly reduced pulmonary metastatic nodules compared treatment Hank's balanced salt solution HER-2/neu. immunization generation cytotoxic lymphocytes (CTLs), which more reactive against relevant targets than CTLs generated immunized Ld-restricted peptide. The results observed this rapidly lethal suggest be useful modality immunotherapy.