Y90 Radioembolization Combined with Immune Checkpoint Blockade in an Animal Model of Hepatocellular Carcinoma

Project: Research project

Description

Radioembolization for hepatocellular carcinoma (HCC) has demonstrated improved time to progression, quality of life, and survival compared to transarterial chemoembolization. However, therapeutic efficacy in intermediate-stage disease is limited, with median survival of approximately 18 months. There is a critical need for optimizing this treatment to prevent recurrence, prolong survival, and potentially provide curative intent. Immunotherapy, a novel treatment option for cancer, may serve to meet this need. Specifically, immune checkpoint inhibitors targeting programmed cell death 1 (PD-1), have demonstrated efficacy in HCC. The newest agent, nivolumab (anti-PD-1 antibody), has been approved for use in HCC with a response rate of 20% in advanced disease. However, its optimization requires study. The immunomodulatory effects of radiation have demonstrated the potential to be combined synergistically with immune-targeting agents, such as an anti-PD-1 antibody. The objective of this proposal is to characterize the immune response to radioembolization in order to determine the optimal time period in which to initiate immunotherapy. Characterization of this response will determine the most advantageous timing of radioembolization-immunotherapy administration to maximize their combined efficacy. We propose studying these effects in a rat model of HCC.
StatusActive
Effective start/end date10/1/199/30/20

Funding

  • RSNA Research and Education Foundation (Agmt 4/2/2018)

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Hepatocellular Carcinoma
Animal Models
Immunotherapy
Cell Death
Antibodies
Radiation Effects
Therapeutics
Quality of Life
Recurrence
Neoplasms