Directing B7-H3 chimeric antigen receptor T cell homing through IL-8 induces potent antitumor activity against pediatric sarcoma.

ABSTRACT:

Background

Advances in pediatric oncology have occurred for some cancers; however, new therapies for sarcoma have been inadequate. Cellular immunotherapy using chimeric antigen receptor (CAR) T cells has shown dramatic benefits in leukemia, lymphoma, and multiple myeloma but has been far less successful in pediatric solid tumors such as rhabdomyosarcoma (RMS) and osteosarcoma (OS). Balancing issues of "on-target, off-tumor toxicity", investigators have identified B7-H3 as a broadly expressed tumor antigen with otherwise restricted expression on normal tissues. We hypothesized that rapid homing via a chemokine receptor and CAR engagement through B7-H3 would enhance CAR T cell efficacy in solid tumors.

Methods

We generated B7-H3 CAR T cells that also express the Interleukin-8

SUBMITTER: Lake JA 

PROVIDER: S-EPMC11268054 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature