Using isogenic cell lines in vivo as xenografts

The explosion of knowledge regarding the genetic underpinnings of human cancer heralds a new era of Personalized Medicine in the form of targeted therapies. To date, in vivo cell based screening has proven a useful tool in almost all drug development programs. Cells used in such screens are usually harvested from cancer patients that harbor the specific mutation of interest, and whilst well highly characterised PDX models can be immensely powerful tools, as with using Horizon's cell lines in vitro the ability to study the effect of specific mutations can be highly insightful and aid in understanding the specific functions of the molecules being screened.

In colaboration with Crown BioScience, Horizon's isogenic cell lines with mutations in a wide variety of genes including KRAS, PIK3CA, PTEN, IDH1 and p53 were tested as part of Crown's in vivo compound screening program. In a POC study, knock-out of the KRAS G13D allele in the DLD-1 colorectal cancer cell line was shown to lead to low tumorigenicity in nude mice. Comparison with 2D in vitro assays demonstrated that mutant KRAS dependency was only seen in in vivo assays, indicating that isogenic xenograft models can reveal gene addiction not seen in vitro.

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We and our customers have tested a number of different Horizon Cell Lines in xenograft - for example, tumorigenicity of HAP1 cells in immuno-competent mice has been assessed by OncoTest.

Three groups with three female NMRI nu/nu mice each received bilaterial subcutaneous injections (left and right flank) of HAP-1 cells supplied by Haplogen Genomics GmbH (5x105, 1x106, 5x106 cells per injection site). During the 90-day observation phase tumors grew out at 8 of 18 injection sites in 6 out of 9 mice. Their volumes ranged from 111 mm3 to larger than 1700 mm3. The latency period for the onset of tumor growth ranged from 19 to 78 days. No deaths or progressive body weight loss of tumor-bearing mice and no clinical signs were observed.

If you'd like to know more about using Horizon's cell lines in vivo please contact us.

 

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