OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response

Autor: Emma Di Carlo, Mario P. Colombo, Giorgia Gri, Piero Musiani, Elena M. Gallo
Předmět:
CD4-Positive T-Lymphocytes
Graft Rejection
Lung Neoplasms
Cell
Priming (immunology)
CD8-Positive T-Lymphocytes
Ligands
Receptors
Tumor Necrosis Factor

immunology
administration /&/ dosage/genetics/immunology
Mice
Transduction
Genetic

Immunologic
T-Lymphocyte Subsets
Receptors
Tumor Cells
Cultured

CD40
Immunology and Allergy
OX40
Lymphocytes
Inbred BALB C
Mice
Knockout

education.field_of_study
Mice
Inbred BALB C

Membrane Glycoproteins
Cultured
biology
Adjuvants
administration /&/ dosage/genetics/physiology
Animals
Antigen-Presenting Cells

immunology
Antigens

CD27
analysis/metabolism
Antigens

physiology
CD4-Positive T-Lymphocytes

immunology
CD8-Positive T-Lymphocytes

immunology
Cancer Vaccines

administration /&/ dosage/genetics/immunology
Female
Gene Targeting
Graft Rejection

genetics/immunology
Granulocyte-Macrophage Colony-Stimulating Factor

administration /&/ dosage/genetics/physiology
Ligands
Lung Neoplasms

secondary/therapy
Lymphocyte Depletion
Lymphocytes

Tumor-Infiltrating
immunology/metabolism
Membrane Glycoproteins

administration /&/ dosage/genetics/physiology
Mice
Mice

Inbred BALB C
Mice

Knockout
Neoplasm Transplantation
Receptors

OX40
Receptors

Tumor Necrosis Factor
Signal Transduction

genetics/immunology
T-Lymphocyte Subsets

immunology
Transduction

Genetic
Tumor Cells

immunology/transplantation
Tumor Necrosis Factors

analysis/metabolism
immunology/transplantation
Tumor Cells
medicine.anatomical_structure
Gene Targeting
Tumor Necrosis Factors
lipids (amino acids
peptides
and proteins)

Tumor necrosis factor alpha
Female
secondary/therapy
Signal Transduction
endocrine system
T cell
Knockout
Antigen-Presenting Cells
OX40 Ligand
Cancer Vaccines
Lymphocyte Depletion
Transduction
Lymphocytes
Tumor-Infiltrating

Adjuvants
Immunologic

Genetic
immunology/metabolism
medicine
Animals
CD40 Antigens
Antigens
education
administration /&/ dosage/genetics/physiology
Granulocyte-Macrophage Colony-Stimulating Factor
Receptors
OX40

OX40 ligand
Tumor Necrosis Factor Receptor Superfamily
Member 7

genetics/immunology
CTL
Immunology
physiology
biology.protein
Cancer research
Tumor Necrosis Factor
CD8
Neoplasm Transplantation
Zdroj: Scopus-Elsevier
Popis: Efficient T cell priming by GM-CSF and CD40 ligand double-transduced C26 murine colon carcinoma is not sufficient to cure metastases in a therapeutic setting. To determine whether a cellular vaccine that interacts directly with both APC and T cells in vivo might be superior, we generated C26 carcinoma cells transduced with the T cell costimulatory molecule OX40 ligand (OX40L) either alone (C26/OX40L) or together with GM-CSF (C26/GM/OX40L), which is known to activate APC. Mice injected with C26/OX40L cells displayed only a delay in tumor growth, while the C26/GM/OX40L tumor regressed in 85% of mice. Tumor rejection required granulocytes, CD4+, CD8+ T cells, and APC-mediated CD40-CD40 ligand cosignaling, but not IFN-γ or IL-12 as shown using subset-depleted and knockout (KO) mice. CD40KO mice primed with C26/GM/OX40L cells failed to mount a CTL response, and T cells infiltrating the C26/GM/OX40L tumor were OX40 negative, suggesting an impairment in APC-T cell cross-talk in CD40KO mice. Indeed, CD4+ T cell-depleted mice failed to mount any CTL activity against the C26 tumor, while treatment with agonistic mAb to CD40, which acts on APC, bypassed the requirement for CD4+ T cells and restored CTL activation. C26/GM/OX40L cells cured 83% of mice bearing lung metastases, whereas C26/OX40L or C26/GM vaccination cured only 28 and 16% of mice, respectively. These results indicate the synergistic activity of OX40L and GM-CSF in a therapeutic setting.
Databáze: OpenAIRE
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