Pilot Study of Intratumoral Injection of Dendritic Cells After High-Dose Conformal External Beam Radiotherapy in Patients with Unresectable Liver Cancer

Lay summary

Hepatocellular cancer (HCC), which occurs in liver tissue, is a common cancer worldwide and a leading cause of cancer-related deaths. Cholangiocarcinoma (CCA), a cancer of the bile ducts (tubes that carry digestive fluid bile within the liver), is a leading cause of primary liver cancer. While curative treatments by surgical resection, liver transplantation or liver-directed ablation therapies are appropriate for patients with early-stage disease, most patients aren't candidates for these potentially curative therapies, and the survival outcome remains dismal.

Thus, there is an unmet need for novel therapies for patients with incurable liver cancer. Growing evidence points to the role of the immune system in developing many cancers, including liver cancer. A function of the immune system is to recognize and destroy cancer cells, but these cells can develop an ability to hide from the immune system or disable the immune system from acting against them. Researchers have developed strategies aimed at boosting the immune system's ability to recognize and kill cancer cells.

The goal of this study in the Hepatobiliary SPORE's Career Enhancement Program is to isolate immature immune cells that can suppress the ability of the immune system to attack cancer from a patient's own blood, transform these immune-suppressive cells into potent immune-stimulatory dendritic cells in the laboratory, and then inject them back directly into the patient's liver tumor. These cells are injected after the patient's tumor has been exposed to radiation therapy. This process causes cancer cell death and the release of tumor-specific proteins that will be recognized and attacked by the injected antitumor immune cells.

This novel approach is expected to lead to maximal tumor killing, durable clinical benefit and overall improved outcomes for patients with unresectable primary liver cancer. This study has the potential to change the trajectory of liver cancer and offers optimism to patients facing a grim outcome.

Head and shoulders photograph of Lionel Aurelien (Lionel) A. Kankeu Fonkoua, M.D.

Lionel Aurelien (Lionel) A. Kankeu Fonkoua, M.D.
2021-2022 awardee

Abstract

The overall objective of this study is to evaluate the therapeutic effects of and characterize the immune response to external beam radiotherapy (EBRT) and an in situ tumor vaccine mediated by dendritic cells (DCs).

Given the ability of external beam radiotherapy to induce immunogenic cell death and elicit tumor-specific immune response, our central hypothesis is that EBRT combined with a dendritic cell vaccine will safely enhance DC priming of T cells with anti-tumor antigens and induce tumor-specific immunity, thereby improving clinical outcomes.

The work proposed in this application is innovative because it takes advantage of a novel and reliable method of dendritic cell purification developed by the Immune, Progenitor and Cell Therapeutics (IMPACT) Laboratory within the Department of Laboratory Medicine and Pathology at Mayo Clinic and because it capitalizes on the avoidance of the immune suppressive potential of DCs by first isolating the monocytes and then culturing them to generate potent immune stimulatory DCs for intratumoral injection.