Primary Cancer Cell System Used for Potential Individualized Therapy

Cancer converts normal body cells into their malignant counterparts, which then need to continue replicating in any possible way. Insights into the disease provide the possibility for more effective therapies with fewer side effects. The new PromoCell Primary Cancer Culture System, for example, enables scientists to develop high-fidelity in vitro models of primary tumors.

Scientists want to use a tumor sample taken from a patient to find the drug that will specifically affect their malignant cells: this is the vision of personalized cancer therapy. There are no side effects for this drug as it only affects the cancer cells. Personalized medicine at this stage is still a dream. However, researchers are finding more and more cues that could eventually enable the individualized treatment of patients.

More than one-quarter of the total number of deaths in the EU (Eurostat, 2013) are due to cancer, and hence there is a vital need for more innovative, tolerable, and effective therapies. Within the last 10 years, cancer chemotherapy has developed from non-specific drugs that destroy the normal cells as well as the tumor, to more specific agents and immunotherapeutic strategies, which could exhibit greater effectiveness with less toxicity (Schilsky et al., 2010).

Wide-Spread Models for Cancer Research Show Several Limitations

To choose the optimal drug for each patient, insights into cancer's biology and molecular profile, and well-established pre-clinical tests are required. It is vital to be able to transfer results from the lab to clinical studies and further (Mitra et al., 2013).

The most accessible and easily usable models for investigating cancer biology and exploring the efficacy of anticancer drugs are immortalized cancer cell lines. But they poorly represent the heterogeneity of tumors in patients, and are therefore not ideal for drug screening.

Julia Schnappinger, Postgraduate Researcher, Immunoanalytics Core Facility, Helmholtz Zentrum in Munich.

Fighting cancer with the body’s own weapons: Julia Schnappinger at the Helmholtz Zentrum in Munich investigates the properties of tumor-infiltrating lymphocytes in patients with renal cell carcinoma. Her research could lead to new immunological cancer therapies.

Fighting cancer with the body’s own weapons: Julia Schnappinger at the Helmholtz Zentrum in Munich investigates the properties of tumor-infiltrating lymphocytes in patients with renal cell carcinoma. Her research could lead to new immunological cancer therapies.

Due to genetic and epigenetic variability, each patient can respond differently to the same drug. Furthermore, the cancer cells reveal accumulations of genetic aberrations with increasing passage number, rather than revealing the behavior of tumors in vivo; since they have a long history of selection and adaptation to a variety of in vitro conditions.

To obtain an enhanced picture of human cancer biology and metastatic progression in vivo, tumor tissue can be engrafted in immunodeficient rodents and cultured via serial transplantation, resulting in stable tumor cell populations. Xenografts from patients with pancreatic adenocarcinoma for example, were found to steadily preserve metastatic potential, tumor morphology, and genetic stability (Delitto et al., 2015). Analogous findings were also reported for xenografts from patients with colon cancer (Dangles-Marie et al., 2007), small-cell lung cancer (Daniel et al., 2009), breast cancer (Morton et al., 2007) and many other types of tumors of a lower grade of malignancy.

However, using animal models needs vast resources, takes up a significant amount of time, lacks up-to-date standardized criteria, and may not even turn out to be advantageous for cancer patients. Furthermore, the progression of the tumor microenvironment is not characterized well, since murine stromal components are included in the xenograft. This is of significance, particularly when analyzing drugs targeting the tumor environment or the immune system, since the biological responses do vary from mouse to humans (Tentler et al., 2012).

Primary Cancer Cell Cultures in Personalized Cancer Therapy

For a patient-specific therapeutic strategy, the use of primary cancer cell cultures is becoming increasingly significant. In fact, it is very important for identifying novel biomarkers, studying tumor biology, and testing new compounds. To date, the isolation and culture of solid tumor cells in vitro still poses a crucial challenge. Conventional tumor cell media usually promote the growth of benign tumor cells, and a stromal overgrowth usually leads to a steady loss of the original malignant cell population. Furthermore, in vitro primary cell cultures are usually temporary and cause a progressive loss of viable tumor cells.

We were trying to establish primary cell cultures from patients with renal cell carcinoma,” stated Julia Schnappinger, “but after three to seven days we could observe cancer cells starting to die, and a necrotic area beginning to form in the center of the tumor spheroids. Other groups tried using self-developed conditioned media with supernatants from other cell lines and growth factors. We were looking for an easier and ready-to-use solution that could help us save time and have better success rates.

Due to this, Schnappinger has been searching for a culture system that enables her to preserve tumor cells in culture for a prolonged period.

Primary cancer cells from a squamous cell carcinoma in vitro: The primary culture was obtained after 4 weeks as compact and heterogeneous adherent colonies formed by different types of epithelial-like cells. The culture proliferated in the Primary Cancer Culture System with a population doubling time of approximately 7 days and could be serially passaged with no signs of growth inhibition.

Primary cancer cells from a squamous cell carcinoma in vitro: The primary culture was obtained after 4 weeks as compact and heterogeneous adherent colonies formed by different types of epithelial-like cells. The culture proliferated in the Primary Cancer Culture System with a population doubling time of approximately 7 days and could be serially passaged with no signs of growth inhibition.

Primary cancer cells from a low-grade small cell lung cancer in vitro: The primary isolate was obtained after 4 weeks as a floating sphere-forming culture, which persisted in a near-quiescent state even after 6 months. The culture proliferated in the Primary Cancer Culture System.

Primary cancer cells from a low-grade small cell lung cancer in vitro: The primary isolate was obtained after 4 weeks as a floating sphere-forming culture, which persisted in a near-quiescent state even after 6 months. The culture proliferated in the Primary Cancer Culture System.

The New PromoCell Culture System Enables Primary Cultures of Human Malignancies

To enable the introduction of long-term cancer cell primary cultures from all kinds of malignant solid tumors, independently of their stage or origin, PromoCell developed the Primary Cancer Culture System.

The development of this culture system took almost two years. We needed to find factors that favor the growth of tumor cells and limit the expansion of benign cells without causing a selection stress that is too strong.

Christian Gojak, Cells and Media Expert, PromoCell.

This culture system provides a widely applicable and economical solution with a distinct and animal-free culture environment, without requiring cytotoxic agents. It promotes the culture and the enrichment of malignant cells but does not promote the growth of benign cells. Therefore, culture conditions are selective for cancer cells, while retaining the original diversity of the cancerous subpopulations. The choice is on the basis of functional properties, and successive cell sorting is not required.

I felt relieved when we started using the PromoCell Primary Cancer Culture System, and we could easily establish primary cancer cell cultures from a patient with renal cell carcinoma. I felt I made a big step forward in my research. However, you should still keep an eye on your cancer cells and their growth patterns. Some types build adherent, two-dimensional colonies, whereas others build three-dimensional spheres. And cancer cells do not proliferate very fast—the average doubling time is two to three weeks.

Julia Schnappinger, Postgraduate Researcher, Immunoanalytics Core Facility, Helmholtz Zentrum in Munich.

Schnappinger’s application of the Primary Cancer Culture System involves incorporating tumor-infiltrating lymphocytes (TILs) to the primary cell culture, allowing them to migrate into the tumor, and examining eventual variations in the phenotype. The question that entices her is to “use the body’s own defenses” and to tune the patient’s immune system to trigger a reaction against the cancer cells. TILs are the effector cells of the immune system in the cancer environment.

It is important to better characterize those cells in patients’ samples, and understand why they are different from circulating lymphocytes and from cells that are present in healthy tissue,” she explained.

Selective culture of primary human cancer cells: The PromoCell Primary Cancer Culture System makes it possible to reliably deplete benign cells from the cell culture while supporting the maintenance of cancer cells and tumor cell heterogeneity.

Pros and cons of primary cancer cell culture: Comparison of primary cancer cell culture with the Primary Cancer Culture System, patient-derived xenografts (PDX), and cancer cell lines. The biological features and limitations, as well as the culture conditions of the different methods of cancer cell culture, are contrasted in the table. Furthermore, the differences in selection properties and further applications of the Primary Cancer Culture System are shown.

The selective culture of primary human cancer cells: The PromoCell Primary Cancer Culture System makes it possible to reliably deplete benign cells from the cell culture while supporting the maintenance of cancer cells and tumor cell heterogeneity. The establishment of cancer cell lines is optionally indicated.​

The successful production of primary tumor cell cultures is crucial for the investigation of stage- and patient-specific therapies, and for improving the effectiveness of traditional clinical approaches. Furthermore, this production enables scientists to enhance the efficiency of drug development, decreases therapy-related toxicity, and yields improved results for the patients.

About PromoCell

Advances in science and medicine are powered by human endeavor. PromoCell empowers your biomedical research. We are your partners for primary cells and cell culture media, as well as for cell biology research. Our portfolio comprises more than 7,000 products that follow the strictest ethical and quality standards.

With more than 28 years of experience in human primary cell culture, we deliver research tools for scientists worldwide. Because sharing knowledge is key to scientific discovery, we also offer professional training at our PromoCell Academy. Our team of experts is by your side in your quest for new therapies.


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Last updated: May 21, 2019 at 10:09 AM

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