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Organoids Developed for Precision Cancer Treatments

T-cells illustration

T-cells (NASA.gov)

22 Jan. 2020. A medical engineering team developed personalized organoid lab models with cancer cells that predict patient responses and may even replace immunotherapy drugs. Researchers from Wake Forest University and medical center in Winston-Salem, North Carolina describe their organoids and results in last month’s issue of the journal Annals of Surgical Oncology (paid subscription required).

The team led by Wake Forest surgery professor Konstantinos Votanopoulos and biomedical engineering professor Aleksander Skardal, now at Ohio State University, are seeking better tools for screening immunotherapy drugs to treat patients with cancer. Immunotherapies are treatments that invoke the immune system to attack disease-causing cells in much the same way the immune system responds to invading pathogens, like bacteria or viruses. Cancer cells, however, are more complex and often influenced by other mechanisms in the body, making immunotherapies a hit-or-miss strategy for many patients.

In addition, notes Skardal in a Wake Forest statement, “Immunotherapy drugs are not inexpensive, and it is not uncommon for the cost of therapy to be measured in millions of dollars per patient.” To help patients and their doctors decide if an immunotherapy will work, the researchers developed organoid models with the patient’s own cancer cells to test proposed drugs.

In 2018, many of the same researchers from Wake Forest’s Organoid Research Center created organoids grown in the lab from a patient’s tumor tissue biopsies to screen chemotherapy drugs. In the new project, the team extended the technology to test for a proposed drug’s ability to invoke an immune response that attacks tumor cells. The three-dimensional organoids contain a patient’s cancer cells, in this case melanoma tumors from patients where the cancer already spread to their lymph nodes or to other parts of the body. The cancer cells are combined with samples from the patient’s lymph nodes and white blood cells, including immune-system cells, and extracellular matrix, the framework material that gives cells their structure.

The Wake Forest team took 10 cellular sample sets from eight melanoma patients, then fabricated this mix into organoids with a water-based polymer hydrogel for each patient. The researchers report it takes about one week for organoids to form followed by a 72-hour incubation period, and the team successfully created organoids for 90 percent of the samples. Samples from seven of the patients included lymph node cells, from which organoids were used to test for an immune response, and 85 percent of the organoids responded similarly to the patients’ subsequent immunotherapy treatments.

In a separate test, the researchers circulated immune-system T-cells from the patients’ white blood cells through the organoids, creating a cancer-killing environment for each patient. The team then transferred the trained T-cells from the immune-enhanced organoids to untrained patient-specific tumor organoids that succeeded in killing their cancer cells, without the need for immunotherapy drugs.

The results suggest that organoids may be used to train a patient’s immune system cells to attack cancer cells in the patient. Votanopoulos says the “this is the first time we have used this platform to train the immune system of the patient to directly recognize and kill their own tumor without the use of drugs. Creating such a clinically relevant model has the potential to revolutionize the way we approach both cancer research and cancer care.”

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