Figure 5.

IgG4 accelerated cancer cell growth in three immune potent mouse models. (A, B) Non-cancer-specific IgG4 accelerated breast cancer cell growth. Local inoculation of mouse breast cancer cells (4T1, 1×10⁵ cells per mouse) into immune competent mice (BALB/c, body weight 20 g, n=5) resulted in sizeable tumor masses in 21 days. Local injections of non-cancer-specific IgG4 resulted in tumor masses that doubled the size of those similarly injected with ‘IgG without IgG4’ or with PBS. As there is no direct effect of IgG4 on cancer cell growth (figure 4I), these results clearly demonstrate that IgG4 can effectively promote tumor growth by inhibiting local immunity. (C, D) IgG4, anti-PD-1 (nivolumab) and anti-PD-1-Fc induced significant tumor (CT26 mouse colon cancer) progression in mice. Five groups of mice were tested by injecting IgG4, nivolumab (IgG4 subtype), nivolumab-Fc, IgG1 and PBS. By 19 days, IgG4, nivolumab and nivolumab-Fc induced significant progression of tumor size in comparison with the other groups. (E–G) IgG4 significantly accelerated skin papilloma formation in a carcinogen-induced skin tumor model in immune potent mice. IgG4 significantly accelerated tumor development and growth in comparison with control (PBS), which in turn had more tumor formation than the group treated with IVIG without IgG4. By 12 weeks, the total tumor volume in IgG4-treated group was more than 12 times larger than the group that was treated with IVIG without IgG4, and was six times larger than the group treated with PBS. (E) The removed back skin of mice from the three groups (at 15 weeks). The tumors are shown in dark-brown color. (F) Tumors at higher magnification. (G) Changes of tumor numbers and volume over time of the three groups. (H) Total tumor volumes of the three groups at 12 weeks after treatment. *p<0.05, **p<0.01, ***p<0.001. IVIG, intravenous IgG; PBS, phosphate buffered saline; PD-1, programmed cell death-1.