Enhancement of radiation therapy by tumor necrosis factor alpha in human colon cancer using a bispecific antibody

Potentiation of ionising radiation by targeting tumour necrosis factor alpha using a bispecific antibody in human pancreatic cancer

“…In the first part of our study, we demonstrated direct cytotoxicity of TNFa on BxPC-3 cells in culture using a clonogenic assay: TNFa-treated BxPC-3 cells showed reduced plating efficiency (Figure 1), confirming that TNFa can be tumoristatic or tumoricidal as described for a variety of neoplastic cell types (Hallahan et al, 1990;Manetta et al, 1990;Gridley et al, 1994a;Kimura et al, 1999;Azria et al, 2003a). In a time-course experiment After 3 days of treatment, cells were washed and further cultured for 21 days in the absence of the cytokine.…”

“…The current treatment includes a combination of surgery, chemotherapy, and radiation without any major improvement in survival (Azria et al, 2002). Over 10 years ago, it was hypothesised that TNFa could increase tumour response to radiation through stimulation of the host antitumour immune responses, direct tumour-cell kill, or through the increase in tumour-cell sensitivity to radiation (Sersa et al, 1988;Hallahan et al, 1990;Gridley et al, 1994a, b;Kimura et al, 1999;Azria et al, 2003a). However, early clinical trials were generally disappointing, with hypotension and vascular leakage frequently being the doselimiting side effects (Chapman et al, 1987;Sherman et al, 1988).…”

“…Several in vitro clonogenic assays suggest that an additive or a supra-additive interaction may occur between TNFa and ionising radiation (Hallahan et al, 1990;Gridley et al, 1994a;Azria et al, 2003a) as well as an enhancement of the antitumour effect of radiation in some murine and human tumours in vivo (Sersa et al, 1988;Nishiguchi et al, 1990;Gridley et al, 1997;Azria et al, 2003a). The oxidative damage produced by TNFa (Zimmerman et al, 1989) may enhance cellular damage produced by ionising radiation.…”

“…Studies involving regional (Lienard et al, 1992;Mavligit et al, 1992;Lejeune et al, 1998) or intratumoral (van der Schelling et al, 1992) injection of TNFa have demonstrated its potential for cancer therapy, but only when a high enough therapeutic concentration of TNFa was obtained in the tumour with a nontoxic systemic concentration. To overcome this limitation, we used previously a bispecific antibody (BAb) directed against carcinoembryonic antigen (CEA) and TNFa to target this cytokine in human CEA-expressing colorectal carcinoma treated simultaneously with RT (Azria et al, 2003a).…”

New aspects concerning ulcerative colitis and colonic carcinoma: Analysis of levels of neuropeptides, neurotrophins, and TNFalpha/TNFreceptor in plasma and mucosa in parallel with histological evaluation of the intestine

“…50 For the treatment of locally advanced colorectal cancer, it is discussed that treatment with TNF␣ in combination with other treatments may be beneficial. 51 With the exception of BDNF, we found significant differences or tendencies for differences between the groups showing that the levels of the analyzed substances in plasma for UC patients were higher than those for the colonic carcinoma patients. These observations show that there is a higher degree of release into the blood of the substances in UC, presumably reflecting the fact that UC often affects a large part of the colon.…”