TECHNOLOGY.

TumorGenesis technology is based on finding the right media in which to grow the cells. The media can be combined with existing 3D cell culture platforms to provide a more reliable, reproducible, and closer in DNA/RNA and proteomic signatures of the Patient Derived Cancer sample. This is especially important to ovarian cancer (OVC) patients. In the US there are approximately 22,000 new cases of ovarian cancer every year, and every year about 14,000 patients die from the disease and its side effects. Over 60% of the ovarian cancer patients relapse from the standard of care which is a combination of Taxol and Cisplatin or Carboplatin in alternating cycles, intravenous (IV) and intraperitoneal (IP), so one drug is given IV and the second drug is given IP and that cycle repeats for as long as the patient can stand it but usually 8-12 weeks after surgical debulking. Less than 10% of the patients have specific markers that can be treated with biological or small molecule inhibitors that have shown promise in treating OVC. About 40% of OVC patients survive past 10 years and we have yet to see if the specific marker treated patients’ relapse or have higher survival rates.

The question is ‘how can we improve the patient outcomes?’ The promise is developing better models for culturing and screening patient-derived cell lines (PDCL) for efficacy with combinations of new and already approved drugs.

Patient Derived Cell Lines (PDCL)

The patient-derived cell lines (PDCL) have great promise to serve as better models for developing novel therapies and personalized oncology strategies. Unfortunately, standard cancer cell lines (SCCL) are difficult to establish and are limited in number; it is illustrative that during the 65 years since the first human cancer cell line HeLa, only ~ 50 to 100 ovarian and breast cancer lines have been established.

Therefore, most cancer research has been carried out using only a handful of cell lines that have been in culture for decades. For example, ~90% of the published cell line research in breast and ovarian cancer has been carried out using 10 cell lines (5 breast, 5 ovary). Importantly, many of standard cell lines have lost the relevant lineage markers for breast or ovarian tissue. Moreover, both the histopathology, and molecular profile of SCCL xenograft tumors frequently differ from the primary tumors. SCCL also generally lack the intra-tumoral heterogeneity due to clonal selection in vitro. In most cases the histopathological diagnosis of the original tumor from which the SCCL was established is unknown. For example, 12 of the 26 ovarian cancer cell lines available from ATCC/ECACC have no histological subtype information. Furthermore, many of the SCCL were established decades ago and thus the original tissue is not available for comparison. In addition, there are no matched normal cell lines associated with most SCCL lines. As a result, it is impossible to carry out normal vs. cancer differential screens with the existing standard cell line collections.

At TumorGenesis, we have a solution. Medias that can be used to culture difficult ovarian cancer cell lines from patients that retain 95%+ of their original signatures even after multiple expansions (up to 70 cycles of expansion compared to 20 using other media).

TumorGenesis also has access to 98 different ovarian cancer cell lines that have established unique signatures and respond differently to treatment. This new Living Ovarian Cancer Cell bank uses our media and retains not on the signatures of the cancer cells as they replicate, it also retains the histological forms of the tumors as shown here.

Specifically, TumorGenesis’s OCI cell lines retain much more of the profile of the patient samples not just in the in vitro cell culture but also when the tumor samples are placed inside an animal model, they histologically and biologically retain their Patient Derived Cancer Cell profiles.