A WKYMVm-containing combination elicits potent anti-tumor activity in heterotopic cancer animal model.

Abstract

The development of efficient anti-cancer therapy has been a topic of intense interest for several decades. Combined administration of certain molecules and immune cells has been shown to be an effective form of anti-cancer therapy. Here, we examined the effects of administering an immune stimulating peptide (WKYMVm), 5-fluoro-uracil (5-FU), and mature dendritic cells (mDCs) against heterotopic cancer animal model. Administration of the triple combination strongly reduced tumor volume in CT-26-inoculated heterotopic cancer animal model. The induced anti-tumor activity was well correlated with FAS expression, caspase-3 activation, and cancer cell apoptosis. The triple combination treatment caused recruitment of CD8 T lymphocytes and natural killer (NK) cells into the tumor. The production of two cytokines, IFN-γ and IL-12, were strongly stimulated by administration of the triple combination. Depletion of CD8 T lymphocytes or NK cells by administration of anti-CD8 or anti-asialoGM1 antibody inhibited the anti-tumor activity and cytokine production of the triple combination. The triple combination strongly inhibited metastasis of colon cancer cells in a heterotopic cancer animal model as well as in a metastatic cancer animal model, and enhanced the survival rate of the mice model. Adoptive transfer of CD8 T lymphocytes and NK cells further increased the survival rate. Taken together, we suggest that the use of triple combination therapy of WKYMVm, 5-FU, and mDCs may have implications in solid tumor and metastasis treatment.

• Authors: Sang Doo Kim, Ha Young Lee, Jae Woong Shim, Hak Jung Kim, Suk-Hwan Baek, Brian A Zabel, Yoe-Sik Bae
• Journal: PloS one (PLoS One) Vol. 7 Issue 1 Pg. e30522 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22295090 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antineoplastic Agents
• Cancer Vaccines
• Cytokines
• Oligopeptides
• Trp-Lys-Tyr-Met-Val-Met
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, immunology, metabolism, pathology)
• Adjuvants, Immunologic (pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects, immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Cancer Vaccines (pharmacology, therapeutic use)
• Colonic Neoplasms (drug therapy, immunology, metabolism, pathology)
• Cytokines (metabolism)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Drug Interactions
• Fluorouracil (pharmacology, therapeutic use)
• Killer Cells, Natural (drug effects, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasm Metastasis
• Oligopeptides (pharmacology, therapeutic use)
• Survival Rate