Rational design of PD-1-CD28 immunostimulatory fusion proteins for CAR T cell therapy.

ABSTRACT:

Background

In many situations, the therapeutic efficacy of CAR T cells is limited due to immune suppression and poor persistence. Immunostimulatory fusion protein (IFP) constructs have been advanced as a tool to convert suppressive signals into stimulation and thus promote the persistence of T cells, but no universal IFP design has been established so far. We now took advantage of a PD-1-CD28 IFP as a clinically relevant structure to define key determinants of IFP activity.

Methods

We compared different PD-1-CD28 IFP variants in a human leukemia model to assess the impact of distinctive design choices on CAR T cell performance in vitro and a xenograft mouse model.

Results

We observed that IFP constructs that putatively exceed the extracellular length of PD-1 induce T-

SUBMITTER: Lorenzini T 

PROVIDER: S-EPMC10421897 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature