Targeted Delivery of TNF‐Alpha and IFN‐Gamma by Tumor Targeting Peptide Inhibited Orthotopic Colorectal Cancer Growth

Abstract

ObjectiveTo determine the in vivo anti‐tumor activities of TNF‐alpha and IFN‐ gamma given alone or in combination and compare with the effects of their conjugates with tumor targeting peptide in a mouse colorectal tumor model.MethodsA mouse orthotopic colorectal tumor model was established. Treatment was given by a single i.v. injection. Mice were sacrificed and examined for their tumor sizes and other immuno and biological parameters in tumors 7 days after treatment. Apoptosis was determined by the TUNEL assay. Immunotherapeutic response was determined by immunofluorecence using antibodies against T lymphocytes, macrophages and NK cells.ResultsTNF‐alpha and IFN‐gamma showed marginal inhibitory effects on tumor growth, while their conjugates with tumor targeting peptide further decreased tumor sizes. Compared with the treatment with non‐targeted TNF‐alpha plus IFN‐gamma, targeted delivery by the peptide markedly alleviated the systemic toxicity as shown by a significant reduction in mortality after treatment. Moreover, targeted delivery of TNF‐alpha plus IFN‐gamma synergistically and significantly inhibited tumor growth.ConclusionsTargeted delivery of TNF‐alpha plus IFN‐gamma exhibited promising tumoricidal activity and at the same time alleviated the systematic toxicity induced by the immuno‐modulators in mice.Acknowledgements: The study was supported by the Innovation and Technology Support Programme and the General Research Fund from the Innovation and Technology Commission and the Research Grant Council from Hong Kong.