c-Kit-targeting immunotherapy for hereditary melanoma in a mouse model.

Abstract

The role of c-Kit in the development of melanoma was studied in line 304/B6 of RET-transgenic mice, in which melanoma spontaneously develops. In Wv/Wv-RET (304/B6)-transgenic mice, in which c-Kit function was severely impaired, development of melanoma was strongly suppressed. Although 31 of the 44 original RET-transgenic mice died of rapidly growing melanoma within 12 months after birth, only 8 of the 44 Wv/Wv-RET-transgenic mice developed slowly growing melanocytic tumors with a greatly prolonged mean tumor-free period, 2 of which died of melanoma at a late stage. Even Wv/+-RET-transgenic mice had a clearly prolonged tumor-free period and definitely reduced frequency (6 of 61) of tumor death within 12 months after birth. Melanin production in the skin of these mice was not strongly impaired, suggesting that c-Kit affects the development of melanomas in these mice with only minor effects in melanin production. c-Kit expression in skin soon after birth was promoted in RET-transgenic mice, and c-Kit was expressed at high levels at the benign but not malignant stage of the tumor. A single injection of anti-c-Kit antibody (ACK2) into RET-transgenic mice soon after birth caused a surprisingly long-lasting suppression of development of melanoma, greatly prolonging the tumor-free period, and none of the 28 ACK2-treated RET-transgenic mice died from tumors at 12 months of age. The c-Kit function needed for melanin production was also suppressed for an unusually long time in ACK2-treated, RET-transgenic mice. These results suggest that c-Kit can be a unique target molecule for melanoma treatment.

• Authors: Masashi Kato, Kozue Takeda, Yoshiyuki Kawamoto, Toyonori Tsuzuki, Khaled Hossain, Akiko Tamakoshi, Takahiro Kunisada, Yasuhiro Kambayashi, Keiki Ogino, Haruhiko Suzuki, Masahide Takahashi, Izumi Nakashima
• Journal: Cancer research (Cancer Res) Vol. 64 Issue 3 Pg. 801-6 (Feb 01 2004) ISSN: 0008-5472 [Print] United States
• PMID: 14871802 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Drosophila Proteins
• Proto-Oncogene Proteins c-kit
• Proto-Oncogene Proteins c-ret
• Receptor Protein-Tyrosine Kinases
• Ret protein, Drosophila

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacology)
• Disease Models, Animal
• Drosophila Proteins (genetics)
• Immunization, Passive (methods)
• Melanoma, Experimental (genetics, immunology, prevention & control)
• Mice
• Mice, Transgenic
• Proto-Oncogene Proteins c-kit (biosynthesis, genetics, immunology)
• Proto-Oncogene Proteins c-ret
• Receptor Protein-Tyrosine Kinases (genetics)