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Vaccine ; 22(27-28): 3585-94, 2004 Sep 09.
Article in English | MEDLINE | ID: mdl-15315837

ABSTRACT

OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Cancer Vaccines/therapeutic use , Membrane Glycoproteins/therapeutic use , Neoplasms, Experimental/immunology , Neoplasms, Experimental/therapy , Animals , Antineoplastic Agents/administration & dosage , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Division/drug effects , Cell Line , Cell Line, Tumor , Female , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Injections, Intraperitoneal , Membrane Glycoproteins/administration & dosage , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , OX40 Ligand , Simplexvirus/genetics , Simplexvirus/immunology , Spleen/cytology , Spleen/immunology , T-Lymphocytes, Cytotoxic/immunology , Tumor Necrosis Factors
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