Severe combined immunodeficiency mice

In vivo studies were carried on the aziridinated cyclopent[Z ]indole quinone out before it was discovered that the aziridinyl ring did not participate in DNA alkylation. The results in Fig. 7.22 for the B16 melanoma syngraft model reveal that there was substantial reduction of tumor mass at 3 mg/kg. However, toxicity (animal deaths) became apparent at 5 mg/kg. On the other hand, human lung cancer xenografts in SCID (severe combined immunodeficient) mice were reduced to 50% mass with 3x1 mg/kg doses without any animal deaths. 

Two types of antibody libraries can be constructed, immune or non-immune. Immune libraries are constructed by immunizing the animal of interest with an antigen(s). In the case of humans, the source can be volunteers with the disease or condition under study (Persson et al., 1991). Human antibodies have also been obtained from severe combined immunodeficiency mice populated with human peripheral blood... 

Maczek C, Bock G, Jurgens G, Schonitzer D, Dietrich H, Wick G (1998) Environmental influence on age-related changes of human lymphocyte membrane viscosity using severe combined immunodeficiency mice as an in vivo model. Exp Gerontol 33(5) 485—498... 

Roth, M.D. et al., Cocaine enhances human immunodeficiency virus replication in a model of severe combined immunodeficient mice implanted with human peripheral blood leukocytes, J. Infect. Dis., 185, 701, 2002. 

SCID mice, severe combined immunodeficient mice... 

Figure 20.3 Heterogeneous distribution of liposomes in tumor tissues. Human colon adenocarcinoma cells (LS174T) were transplanted in dorsal skinfold chambers in severe combined immunodeficient mice. Fifteen to 32 days post tumor cell transplantation, fluorescently labeled liposomes were injected intravenously. The photos were taken at two days post injections. Liposomes accumulated only in perivascular regions in solid tumors. The arrows indicate liposomes internalized by cells. Iiar=100um. Reproduced with permission (Yuan etal., 1994).

Tanaka K, Tanaka M, Igarashi S, Onodera O, Miyatake T, Tsuji S. Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti-Yo antibody. 2. Passive transfer of murine mononuclear cells activated with recombinant Yo protein to paraneoplastic cerebellar degeneration lymphocytes in severe combined immunodeficiency mice. Clin Neurol Neurosurg 1995 97(1) 101-105. 

In another study by Wang et al., i.v. injection of liposomes carrying rat insulin promoter (RIK)-thymidine kinase (TK) was found to be less toxic to the liver than the i.p. injection of the same formulation to severe combined immunodeficient mice (SCID) [192], The direct injection of the liposomes to abdominal cavity probably leads to higher local absorption and, thus, higher liver toxicity. In contrast, the i.v. injected volume is smaller (70 pL to 100pL of i.p. injection), which is diluted fast as soon as it enters the body. 

Garofalo A., Chriivi R. G. S., Scanziani E., Mayo J. G., Vecchi A. and Giavazzi R. (1993). Comparative study on the metastatic behavior of human tumors in nude, beige/nude/Xid and severe combined immunodeficient mice. Invasion Metastasis 13, 82-91. 

Ochakovskaya R, Osorio L, Goldenberg DM, Mattes MJ. Therapy of disseminated B-cell lymphoma xenografts in severe combined immunodeficient mice with an anti-CD74 antibody conjugated with Indium, 67Gal-lium, or °Yttrium. Clin Cancer Res 2001 7 1505-1510. 

TABLE 10.1-5 Examples of the Application of Severe Combined Immunodeficiency Mice... 

Dolman CS, Mueller BM, Lode HN, Xiang R, Gillies SD, Reisfeld RA. Suppression of human prostate carcinoma metastases in severe combined immunodeficient mice by interleukin 2 immunocytokine therapy. Clin Cancer Res 1998 4 2551-2557. 

Retroviral-mediated transduction of liTERT (human telomerase reverse transcriptase) in human dermal microvascular endothelial cells (EC) (HDMEC) results in cell hues that form microvasculai stractures upon subcutaneous implantation in severe combined immunodeficiency mice (SCID) mice. Anti-human type IV collagen basement membrane immu-noreactivity and visualization of enhanced green fluorescent protein (eGEP)-labeled microvessels confiimed the human origin of these vessels. Piimaiy HDMEC-derived vessel density decreased with time, while telomerized HDMEC maintained durable vessels six... 

B. Frerich, K. Winter, K. ScheHa-, U.D. Braumann, Comparison of different fabrication techniques for human adipose tissue engineering in severe combined immunodeficient mice, Artif. Organs 36 (2012)... 

Steams ME, Amatangelo MD, Varma D, Sell C, Goodyear SM (2010) Combination thtaapy with epigallocatechin-3-gallate and doxorubicin in human prostate tumor modeling studies inhibition of metastatic tumor growth in severe combined immunodeficiency mice. Am J Pathol 177 3169-3179... 

The most common application of BLI in cancer research is the use of stably transfected, luciferase expressing mmor cell lines where the luciferase signal is used as a measure of tumor burden and metastasis (55). The first example of this approach used the human cervical carcinoma cell line, HeLa (56,57). HeLa cells labeled with luciferase were injected into severe combined immunodeficient mice via the tail vein, and cells were immediately apparent in the lung. This model has since been used to examine lung colonization by several tumor cell lines. These, and now many other studies, have demonstrated that luciferase expression correlates with tumor burden through the use of many ex vivo assays and through the use of other imaging modalities (25,56,57). 

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