Granulocyte-Macrophage Colony-Stimulating Factor-Based Melanoma Cell Vaccines Immunize Syngeneic and Allogeneic Recipients via Host Dendritic Cells

Abstract

Subcutaneous injection of GM-CSF-expressing cancer cells into experimental animals results in protective cancer immunity. To delineate the mode of action of such vaccines, we used trinitrophenyl, the antigenic moiety of the contact allergen trinitrochlorobenzene, as surrogate Ag. Trinitrophenyl-derivatized bone marrow-derived dendritic cells were found to elicit a contact hypersensitivity response in syngeneic, but not in allogeneic recipients, compatible with their expected mode of direct Ag presentation. When expressing GM-CSF, haptenized M3 melanoma cells were also able to induce a contact hypersensitivity response but, in contrast to bone marrow-derived dendritic cells, not only in syngeneic but also in allogeneic recipients. This argues for a critical role of host APC. To identify their nature, we introduced the β-galactosidase (βgal) gene into M3-GM cells. Their administration activated βgal-specific, Ld-restricted CTL in syngeneic BALB/c mice. Evaluation of lymph nodes draining M3-GM-βgal injection sites revealed the presence of cells presenting the respective Ld-binding βgal peptide epitope. Based on their capacity to activate βgal-specific CTL, they were identified as being CD11c+ dendritic cells. These experiments provide a rational basis for the use of GM-CSF-based melanoma cell vaccines in an allogeneic setting.

Selective impairment in dendritic cell function and altered antigen‐specific CD8+ T‐cell responses in diet‐induced obese mice infected with influenza virus

“…The purity of the CD11c + population was assessed by flow cytometry and found to be 76%. About 20% of the population was composed of CD11c ) B220 + cells, probably B cells, 25 which have been shown to be poor stimulators of T cells when antigen is not continuously present in the stimulation culture. 26 T cells were isolated from spleens of lean mice that had been infected with influenza 7 days previously.…”

Dendritic cells and melanoma tumorigenesis: An insight

“…Upon administration into animals, the vaccine can induce an antigen-specific CTL against the tumor. 39 In melanoma, the therapeutic potential of DCs is supported by several observations including: (1) DCs expressing certain cytokines (IL-2 or IL-12) can induce antitumor responses against poorly immunogenic B16F10 melanoma cells, 40 (2) peptide-loaded DCs can elicit melanoma-associated CTL response in vitro, 41 (3) DCs loaded with killed melanoma cells can prime naive T cells against the melanoma associated antigens, 42 (4) DCs, genetically engineered to express melanoma associated Ags, can process and present these Ags and therefore induce specific CTL response, 43 (5) DCs can process Ags from autologous melanoma apoptotic bodies and induce effector T cells in melanoma patients. 44 In this regard, mature DCs containing apoptotic melanoma cells can cross-present melanoma antigens to CTL, generating a specific CTL response.…”

“…DCs of myeloid lineage associate with T lymphocytes within lymphoid tissue. The DCs of myeloid and lymphoid precursors provide critical antigen presenting cells (APCs) activity for initiating specific T-lymphocyte activation and proliferation [3][4][5] (Fig. 1C).…”

Dendritic cells in the skin – potential use for melanoma treatment

“…For optimization of the host‐specific immune response, several models of multimodal immunotherapy have been reported, including cytokine‐based melanoma cell vaccines (Moller et al., 2000; Schneeberger et al., 2003; Schreiber et al., 1999; Tuettenberg et al., 2007). Also, combined antibody‐mediated blockade of CTLA‐4, expressed on the surface of activated T‐lymphocytes, and DC‐based vaccine are other strategies that might be applied in the future (Cranmer and Hersh, 2007).…”