Effect of an anti-human Co-029/tspan8 mouse monoclonal antibody on tumor growth in a nude mouse model

Abstract

New therapeutic agents are needed in digestive tract tumors. Co-029/tspan8 is a tetraspanin frequently expressed on human colorectal tumors, In this work, we report the effects of the monoclonal antibody Ts29.2, targeting Co-029/tspan8, on colorectal tumor cells in vitro and after implantation in nude mice. HT29, Isreco1 and SW480 colorectal tumor cell lines were used for this study. HT29 has a strong endogenous expression of Co-029/tspan8, whereas Isreco1 cells don't express Co-029/tspan8 and SW480 has only a weak expression. Isreco1 and SW480 were transduced to express Co-029/tspan8 at the same level as HT29. In order to check the specificity of the effect of monoclonal antibody Ts29.2, low Co-029/tspan8 expressing SW480 cells were injected simultaneously with transduced cells in the back, on the left and right sides of the mice. With an early treatment, Ts29.2 mAb inhibited growth of tumors expressing Co-029/tspan8 up to 70%, whereas a delayed treatment was less efficient. No effect of the antibody on cell proliferation or apoptosis induction was detected in vitro. No increase of activated caspase 3 labeling was observed in vivo and areas occupied by vessels were not significantly different between treated mice and controls. This suggests that the action of Ts29.2 is linked neither to cellular toxicity nor to the inhibition of the previously reported angiogenic properties of Co-029/tspan8. An inhibition of cell proliferation in vivo is demonstrated by a reduction of the mitotic index in HT29 tumors of Ts29.2 treated mice. The discrepancy between in vitro and in vivo data on cell proliferation suggests that the binding of Ts29.2 to tumor cells may modify their response to signals issued from the microenvironment. Given the restricted pattern of tissue expression of the tetraspanin Co-029/tspan8, these preliminary results put forth for consideration the antibody targeting of this tetraspanin in further investigations for therapeutic applications.

TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer

“…E-cadherin, claudin, EPCAM, a6b4 integrin, CD44v, and EWI are suggested as key associated transmembrane proteins for TSPAN8, and antibodies against them may block tumor angiogenesis in treating patients with TSPAN8-positive tumors [27]. Actually, Ailane et al [28] reported that in a nude mouse model, a monoclonal antibody against TSPAN8 inhibited the growth of tumors expressing TSPAN8 up to 70 % in vivo, while it did not affect the cell growth in vitro.…”

Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer

“…Here, we address the feasibility of RIT approach by targeting a novel tumor specific antigen: TSPAN8, using the monoclonal antibody Ts29.2 [19]. Indeed, it has been previously shown to exhibit anti-tumor effects on xenograft models.…”

“…This antibody has been previously shown to slow down growth of colon xenograft tumors in nude mice [19]. A non-target, irrelevant IgG2b antibody (16F12) directed against the human Mullerian inhibiting substance type II receptor [41] was provided by Dr Isabelle Navarro-Teulon (Montpellier, France).…”

TSPAN8 as a Novel Emerging Therapeutic Target in Cancer for Monoclonal Antibody Therapy

“…In addition, they reported that this antibody showed a 75% motility reduction of CO-029-overexpressing human colon cancer cells [70]. Ailane et al generated TS29.2, an IgG2b type of TS29, and found that with early treatment, this antibody inhibits the growth of CO-029-overexpressing tumor cells by up to 70% [90]. Stuhlmiiler et al also generated a mouse monoclonal antibody (D6.1) by immunizing athymic nude mice with partially purified human melanoma tumor-associated antigens [91].…”