Human xenografted carcinomas

Fig. 6. In vivo antitumor activity of complex 9 (40 mg/kg) compared to cisplatin 1 (4 mg/kg) against CHlcisR human ovarian carcinoma xenograft. Adapted from 111). 

In mice with human breast carcinoma xenografts, a humanized IgG anti-HER-2 MAb eradicated well-established tumours [58]. In addition, a humanized version of an IgG anti-CD33 MAb (HuM 195) mediated ADCC in vitro [59] and had an 8.6-fold higher avidity than the parent murine Mab. Recombinant antibody fragments may have valnable properties as discnssed above, bnt their biophysical behavionr, prodnction yield and low thermostability leaves mnch to be desired and thereby limits their nsefnlness for in-vivo applications so far [60]. One possibility to improve these characteristics of scFv fragments with snboptimal stability and/or folding yield, is the grafting of their CDRs onto the framework of a different, more stable scFv [61,62]. 

Wolschek MF, Thallinger C, Kursa M et al (2002) Specific systemic nonviral gene delivery to human hepatocellular carcinoma xenografts in SCID mice. Hepatology 36 1106-1114... 

The in vivo antitumor activity of 78 was evaluated against A151 human ovarian carcinoma xenograft in nude athymic mice, and was found to be equivalent or slightly better than that of paclitaxel, causing total regression of the tumor.94... 

Since human breast carcinoma xenografts in nude mice provide the closest available model of human breast cancer, we have compared the effect of EM-800 and tamoxifen alone and in combination on the growth of ZR-75-1 breast cancer xenografts in nude mice. 

Concentration of intact analogues 1 calculated from measured AUC (pg h/mL) after oral administration. Concentration of metabolite 5 -DFUR (9) calculated from measured AUC (pg h/mL) after oral administration. Measured at orally administered doses of 0.13 and 0.67 mmol/kg/day, respectively, over a 21-day interval in mice bearing CXF280 human colon carcinoma xenografts. 

Fig. 2. Comparative antitumor activity of orally administered JM216,135 mg/kg q7dx4 ( ), i.v. administered cisplatin, 3 mg/kg q 7dx4 (A), and i.v. administered carboplatin, 90 mg/kg q7dx4 ( ) to mice bearing the CHI human ovarian carcinoma xenograft (controls, ( ))...

In addition to the extensive oral antitumor studies described above in mice bearing the ADJ/PC6 plasmacytoma and human ovarian carcinoma xenografts, JM216 has also been evaluated in vivo in two murine models of acquired cisplatin resistance. Schedule-dependency effects have also been determined. 

In Vivo Antitumor Properties. Initial studies using intraperitoneal administration of AMD473 at doses of 35-40 mg/kg showed the drug to confer marked antitumor activity against both murine (ADJ/PC6, cf. Table) and human ovarian-carcinoma xenografts [54]. Moreover, activity was observed... 

Significant in vivo antitumor activity by both the intraperitoneal and oral routes against acquired cisplatin-resistant human ovarian-carcinoma xenografts ... 

Reyes, G., Villanueva, A., Garcia, C., Sancho, F. J., Piulats, J., Lluis, F. and Capelld, G. (1996). Orthotopic xenografts of human pancreatic carcinomas acquire genetic aberrations during dissemination in nude mice. Cancer Res. 56, 5713-5719. 

Boven E,VanderVijghWJE, Nauta MM, SchluperHMM,PinedoHM. Comparative activity and distribution studies of five platinium analogues in nude mice bearing human ovarian carcinoma xenografts. Cancer Research, 45 86-90,1985 Gormley PE, Bull JM, EeRoy AF, Cysyk R. Kinetics of cis-dichlorodiammineplatinum. Clin Pharmacol Then 1979 Mar 25[3] 351-7 SiddikZH, Jones M, Boxall FE, Harrap KR. Comparative distribution and excretion of carboplatin and cisplatin in mice Cancer Chemother Pharmacol. 1988 21 [1 ] 19-24... 

Liu M, Bryant MS, Chen J, Lee S, Yaremko B, et al. 1999. Effects of SCH 59228, an orally bioavailable farnesyl protein transferase inhibitor, on the growth of oncogene-transformed fibroblasts and a human colon carcinoma xenograft in nude mice. Cancer Chemother. Pharmacol. 43 50-58... 

B72.3 is a monoclonal antibody developed from the membrane-enriched fraction of breast carcinoma in a patient with hver metastasis. The B72.3 reactive antigen was purified and called TAG-72 (tumor-associated glycoprotein). Further purification of TAG-72 from LS-174T human colon carcinoma xenograft produced a new generation of monoclonal antibodies with higher affinity. These antibodies, denoted cc for "colon carcinoma, were used in subsequent studies. 

Nakase Y, Hagiwara A, Kin S, et al. Intratumoral administration of methotrexate bound to activated carbon particles antitumor effectiveness against human colon carcinoma xenografts and acute toxicity in mice. J Pharmacol Exp Ther 2004 311 382-387. 

Table 2. In vivo cytotoxicity of Ecteinascidins and Eudistomin K against P-388 leukemia, B-16 melanoma, Lewis Lung carcinoma xenograft (LL), M5076 ovarian sarcoma and MX-1 human mammary carcinoma xenograft, doses in pg/kg/day. ...

Boven E, Van der Vijgh WJF, Nauta MM, Schluper HMM, Pinedo HM. Comparative activity and distribution studies of five platinium analogues in nude mice bearing human ovarian carcinoma xenografts. Cancer Res 1985 45 86-90. 

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