Researchers use appendicular cancer organoids to study personalized immunotherapeutic response

Wake Forest researchers and clinicians are using patient-specific tumor organoid models as a preclinical support platform to better assess immunotherapeutic treatment for appendix cancer, one of the rarest cancers affecting only 1 people in 100,000. Immunotherapies, also called biological therapies, activate the body’s immune system to control and kill cancer.

Cancer of the appendix is ​​historically resistant to systemic chemotherapy, and the effect of immunotherapy is essentially unknown because clinical trials are difficult to perform due to the lack of adequate patient numbers, resulting in a lack of data. and limited research models.

Researchers at the Wake Forest Organoid Research Center (WFORCE), a joint venture between the Wake Forest Institute for Regenerative Medicine (WFIRM) and the Wake Forest Comprehensive Cancer Center, were the first to create appendix cancer organoids to be used as predictive model for potential treatment options (published in 2018). The Comprehensive Cancer Center is a major high-volume center with a worldwide reputation in the treatment of appendix cancer.

These cancerous organoids are part of WFIRM’s “Body-on-a-Chip” system that allows scientists to design organoids, or human tissue equivalents, that function very similarly to real human tissues and organs.

In this new study published in the journal Clinical cancer research, their results indicate that various types of immunotherapies tested on organoids can potentially support treatment decisions and can achieve personalized results, identifying beneficial treatments while sparing patients the harmful side effects of drugs for which they will not get any. profit.

For this study, we reconstructed the patients’ tumors as organoids, supercharged by an integrated immune system obtained directly from the patient. In this way, we created a personalized interface to study the effectiveness of immunotherapy drugs in activating a patient’s immune system to kill cancer. This platform innovates for cancer of the appendix, and it can also be applied to the research of other rare cancers for which preclinical models are lacking. “

Konstantinos I. Votanopoulos, MD, PhD, senior author, professor of surgery at the Comprehensive Cancer Center and co-director of WFORCE

This research study uses WFIRM’s “Body-on-a-Chip” system that allows scientists to design organoids, or humanoid tissue equivalents, that function very similarly to real human organs.

Tumor biopsy cells from 26 patients were obtained to grow organoids – tiny 3D tissue-like structures, in the lab that mimic cancerous tumors. Immune-enhancing tumor organoids were treated with one of three immunotherapy drugs and then evaluated for their reactivity.

“In the future, by verifying that the tumor and its organoids behave in the same way, we could change the design of clinical trials and optimize costs by targeting patients with organoids who have shown favorable results,” said Votanopoulos.

Current strategies for understanding tumor progression focus on analyzes of isolated tumor cells, but do not capture the interactions between a tumor and its surrounding space, known as the microenvironment or stroma. This leads to inaccuracies in predicting tumor progression and response to chemotherapy or immunotherapy. Tumor organoids derived from patients are used as a testing and prediction platform to model disease, assess the efficacy and / or toxicity of new and existing drugs, and can be used to test for environmental risks.

Co-author Shay Soker, PhD, professor of regenerative medicine who leads tumor organoid research at WFIRM and co-leads WFORCE, said new technologies and biological models that improve prognosis will have a significant effect on mortality patients. “The use of organoids as a preclinical platform may lead to the development of new therapies that specifically target and control tumor cells, sparing healthy tissues the side effects of chemotherapy and immunotherapy treatments,” he said. . “For rare cancers like appendix cancer, this technology can make a difference in the overall quality of life of patients.”


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