Abstract | BACKGROUND: METHODS: Established subcutaneous Renca-MUC1 tumors were treated with 8 Gy radiation on day 11 and peritumoral injections of MVA-MUC1-IL2 vector on day 12 and 17, or using a reverse sequence of vaccine followed by radiation. Growth delays were monitored by tumor measurements and histological responses were evaluated by immunohistochemistry. Specific immunity was assessed by challenge with Renca-MUC1 cells. Generation of tumor-specific T cells was detected by IFN-γ production from splenocytes stimulated in vitro with tumor lysates using ELISPOT assays. RESULTS:
Tumor growth delays observed by tumor irradiation combined with MVA-MUC1-IL-2 vaccine were significantly more prolonged than those observed by vaccine, radiation, or radiation with MVA empty vector. The sequence of cancer vaccine followed by radiation two days later resulted in 55-58% complete responders and 60% mouse long-term survival. This sequence was more effective than that of radiation followed by vaccine leading to 24-30% complete responders and 30% mouse survival. Responding mice were immune to challenge with Renca-MUC1 cells, indicating the induction of specific tumor immunity. Histology studies of regressing tumors at 1 week after therapy, revealed extensive tumor destruction and a heavy infiltration of CD45+ leukocytes including F4/80+ macrophages, CD8+ cytotoxic T cells and CD4+ helper T cells. The generation of tumor-specific T cells by combined therapy was confirmed by IFN-γ secretion in tumor-stimulated splenocytes. An abscopal effect was measured by rejection of an untreated tumor on the contralateral flank to the tumor treated with radiation and vaccine. CONCLUSIONS:
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Authors | Gilda G Hillman, Lyndsey A Reich, Shoshana E Rothstein, Lisa M Abernathy, Matthew D Fountain, Kali Hankerd, Christopher K Yunker, Joseph T Rakowski, Eric Quemeneur, Philippe Slos |
Journal | Journal for immunotherapy of cancer
(J Immunother Cancer)
Vol. 5
Pg. 4
( 2017)
ISSN: 2051-1426 [Electronic] England |
PMID | 28116088
(Publication Type: Journal Article)
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Chemical References |
- Antigens, Neoplasm
- IL2 protein, human
- Interleukin-2
- MVA vaccine
- Mucin-1
- Vaccines, DNA
- Viral Vaccines
- Interferon-gamma
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Topics |
- Animals
- Antigens, Neoplasm
(genetics, immunology, radiation effects)
- CD8-Positive T-Lymphocytes
(immunology, radiation effects)
- Carcinoma, Renal Cell
(drug therapy, immunology, pathology, radiotherapy)
- Cell Line, Tumor
- Female
- Genetic Vectors
- Interferon-gamma
(genetics, immunology, therapeutic use)
- Interleukin-2
(genetics, immunology, therapeutic use)
- Mice
- Mucin-1
(genetics, immunology, therapeutic use)
- T-Lymphocytes, Cytotoxic
(immunology, radiation effects)
- Vaccines, DNA
- Viral Vaccines
(administration & dosage, immunology)
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