Back to Search
Start Over
Radiocurability by targeting tumor necrosis factor-alpha using a bispecific antibody in carcinoembryonic antigen transgenic mice
- Source :
- International Journal of Radiation Oncology-Biology-Physics, International Journal of Radiation Oncology-Biology-Physics, Elsevier, 2007, 69 (4), pp.1231-7. ⟨10.1016/j.ijrobp.2007.07.2372⟩, International Journal of Radiation Oncology, Biology, Physics, International Journal of Radiation Oncology, Biology, Physics, 2007, 69 (4), pp.1231-7. ⟨10.1016/j.ijrobp.2007.07.2372⟩
- Publication Year :
- 2007
- Publisher :
- HAL CCSD, 2007.
-
Abstract
- International audience; PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) enhances radiotherapy (RT) killing of tumor cells in vitro and in vivo. To overcome systemic side effects, we used a bispecific antibody (BsAb) directed against carcinoembryonic antigen (CEA) and TNF-alpha to target this cytokine in a CEA-expressing colon carcinoma. We report the evaluation of this strategy in immunocompetent CEA-transgenic mice. METHODS AND MATERIALS: The murine CEA-transfected colon carcinoma MC-38 was used for all experiments. In vitro, clonogenic assays were performed after RT alone, TNF-alpha alone, and RT plus TNF-alpha. In vivo, the mice were randomly assigned to treatment groups: control, TNF-alpha, BsAb, BsAb plus TNF-alpha, RT, RT plus TNF-alpha, and RT plus BsAb plus TNF-alpha. Measurements of endogenous TNF-alpha mRNA levels and evaluation of necrosis (histologic evaluation) were assessed per treatment group. RESULTS: In vitro, combined RT plus TNF-alpha resulted in a significant decrease in the survival fraction at 2 Gy compared with RT alone (p < 0.00001). In vivo, we observed a complete response in 5 (50%) of 10, 2 (20%) of 10, 2 (18.2%) of 11, and 0 (0%) of 12 treated mice in the RT plus BsAb plus TNF-alpha, RT plus TNF-alpha, RT alone, and control groups, respectively. This difference was statistically significant when TNF-alpha was targeted with the BsAb (p = 0.03). The addition of exogenous TNF-alpha to RT significantly increased the endogenous TNF-alpha mRNA level, particularly when TNF-alpha was targeted with BsAb (p < 0.01). The percentages of necrotic area were significantly augmented in the RT plus BsAb plus TNF-alpha group. CONCLUSION: These results suggest that targeting TNF-alpha with the BsAb provokes RT curability in a CEA-expressing digestive tumor syngenic model and could be considered as a solid rationale for clinical trials.
- Subjects :
- Cancer Research
Pathology
MESH: Combined Modality Therapy
Necrosis
medicine.medical_treatment
Bispecific antibody
MESH: Random Allocation
Drug Evaluation, Preclinical
Mice
Random Allocation
0302 clinical medicine
Carcinoembryonic antigen
Antibodies, Bispecific
MESH: Immunocompromised Host
MESH: Animals
Tumor Stem Cell Assay
Radiation
biology
MESH: Tumor Stem Cell Assay
synergism
Combined Modality Therapy
3. Good health
Cytokine
Oncology
MESH: Cell Survival
030220 oncology & carcinogenesis
Colonic Neoplasms
MESH: Drug Evaluation, Preclinical
Tumor necrosis factor alpha
Antibody
medicine.symptom
medicine.medical_specialty
MESH: Carcinoembryonic Antigen
Cell Survival
MESH: Mice, Transgenic
Mice, Transgenic
[SDV.CAN]Life Sciences [q-bio]/Cancer
Immunocompromised Host
03 medical and health sciences
CEA-transgenic mice
MESH: Antibodies, Bispecific
[SDV.CAN] Life Sciences [q-bio]/Cancer
Antigen
In vivo
Tumor Necrosis FactorΑ
medicine
Animals
Humans
Radiology, Nuclear Medicine and imaging
RNA, Messenger
Clonogenic assay
MESH: Mice
MESH: RNA, Messenger
MESH: Colonic Neoplasms
MESH: Humans
Tumor Necrosis Factor-alpha
business.industry
radiotherapy enhancement
Carcinoembryonic Antigen
MESH: Tumor Necrosis Factor-alpha
biology.protein
Cancer research
business
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 03603016 and 1879355X
- Database :
- OpenAIRE
- Journal :
- International Journal of Radiation Oncology-Biology-Physics, International Journal of Radiation Oncology-Biology-Physics, Elsevier, 2007, 69 (4), pp.1231-7. ⟨10.1016/j.ijrobp.2007.07.2372⟩, International Journal of Radiation Oncology, Biology, Physics, International Journal of Radiation Oncology, Biology, Physics, 2007, 69 (4), pp.1231-7. ⟨10.1016/j.ijrobp.2007.07.2372⟩
- Accession number :
- edsair.doi.dedup.....8ef7a0afd304a959776e1f38bf032b25
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2007.07.2372⟩