Enhanced antitumor immunity through sequential targeting of PI3Kδ and LAG3.

ABSTRACT:

Background

Despite striking successes, immunotherapies aimed at increasing cancer-specific T cell responses are unsuccessful in most patients with cancer. Inactivating regulatory T cells (Treg) by inhibiting the PI3Kδ signaling enzyme has shown promise in preclinical models of tumor immunity and is currently being tested in early phase clinical trials in solid tumors.

Methods

Mice bearing 4T1 mammary tumors were orally administered a PI3Kδ inhibitor (PI-3065) daily and tumor growth, survival and T cell infiltrate were analyzed in the tumor microenvironment. A second treatment schedule comprised PI3Kδ inhibitor with anti-LAG3 antibodies administered sequentially 10 days later.

Results

As observed in human immunotherapy trials with other agents, immunomodulation by PI3K

SUBMITTER: Lauder SN 

PROVIDER: S-EPMC7583804 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature