Résumé
To overcome the systemic side effects of tumor necrosis factor alpha (TNFα) injected i.v., we used a bispecific antibody (BAb) directed against carcinoembryonic antigen (CEA) and TNFα to target this cytokine in human CEA-expressing colorectal carcinoma treated simultaneously with radiation therapy (RT).
LS174T cell line was used to study the interaction of TNFα and radiation on clonogenic cytotoxicity. When TNFα (2500 U/mL) was added 12 h before RT, the surviving fraction at 2 Gy was 54% lower than that obtained with irradiation alone (0.23 vs. 0.42, respectively,
p = 0.001). At 20%, 50%, or 70% survival, data points were within the envelope of additivity. Concerning
in vivo experiments, RT as a single agent slowed tumor progression as compared with the control group (
p = 0.027), whereas TNFα, BAb, or BAb + TNFα had no effect. BAb + TNFα + RT combination enhanced the delay for the tumor to reach 2000 mm
3 as compared with RT alone (
p = 0.033, for BAb + TNFα + RT group vs. RT group).
These results suggest that TNFα in combination with BAb and RT may be beneficial for the treatment of locally advanced colorectal cancer.