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. 2018 Feb 6;9(17):13623–13636. doi: 10.18632/oncotarget.24426

Figure 4. Trastuzumab gene transfer and trastuzumab protein administration in BALB/c mice.

Figure 4

(A) Impact of hyaluronidase (hyal) pretreatment and administered construct configuration (pCAG-tras-gtGTU, a dual antibody cassette system, vs. pCAG-tras2A-gtGTU, a single 2A-driven antibody expression cassette) on expressed plasma trastuzumab concentrations (*P < 0.05). (B) Dose-response between administered pCAG-tras-gtGTU and expressed plasma trastuzumab concentrations. 150 µg pDNA was equally divided across two tibialis anterior muscles. 15 µg and 75 µg were injected in one tibialis anterior muscle (***P < 0.001, ****P < 0.0001). (C) Anti-trastuzumab antibodies start emerging 10 days after intramuscular (i.m.) electrotransfer of 75 µg pCAG-tras-gtGTU. A second pCAG-tras-gtGTU dose was given 32 days after the first. Presented optical densities (OD) result from 50-fold diluted plasma samples after background subtraction. The figure insert shows the same samples, diluted 25-fold to highlight anti-trastuzumab antibodies in the first two weeks. Data are presented as mean ± standard error of mean. (D) Plasma trastuzumab titers resulting from one or two intravenous (i.v.) injections of 0.2 mg/kg trastuzumab. The first plasma sample post injection was collected after one hour. The arrow indicates the timing of the second i.v. trastuzumab injection.