Anti-tumour therapeutic efficacy of OX40L in murine tumour model

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) carcinom...

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Bibliographic Details
Published in:Vaccine 2004-09, Vol.22 (27), p.3585-3594
Main Authors: Ali, Selman A., Ahmad, Murrium, Lynam, June, McLean, Cornelia S., Entwisle, Claire, Loudon, Peter, Choolun, Esther, McArdle, Stephanie E.B., Li, Geng, Mian, Shahid, Rees, Robert C.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - therapeutic use
Applied microbiology
Biological and medical sciences
Cancer
Cancer Vaccines - therapeutic use
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cell Division - drug effects
Cell growth
Cell Line
Cell Line, Tumor
CTL
Cytokines
Female
Fundamental and applied biological sciences. Psychology
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Immunotherapy
Injections, Intraperitoneal
Ligands
Lymphocytes
Medical sciences
Membrane Glycoproteins - administration & dosage
Membrane Glycoproteins - therapeutic use
Metastasis
Mice
Mice, Inbred BALB C
Microbiology
Neoplasm Transplantation
Neoplasms, Experimental - immunology
Neoplasms, Experimental - therapy
OX40L
Peptides
Proteins
Rodents
Simplexvirus - genetics
Simplexvirus - immunology
Spleen - cytology
Spleen - immunology
T cell receptors
T-Lymphocytes, Cytotoxic - immunology
Tumor Necrosis Factors
Tumors
Vaccination
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
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Summary: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.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2004.03.041