Ontology highlight
ABSTRACT: Purpose
Chimeric antigen receptor (CAR) T-cell therapy has shown great promise for treating hematologic malignancies but requires a long duration of T-cell expansion, is associated with severe toxicity, and has limited efficacy for treating solid tumors. We designed experiments to address those challenges.Experimental design
We generated a cell membrane-anchored and tumor-targeted IL12 (attIL12) to arm peripheral blood mononuclear cells (PBMC) instead of T cells to omit the expansion phase for required CAR T cells.Results
This IL12-based attIL12-PBMC therapy showed significant antitumor efficacy in both heterogeneous osteosarcoma patient-derived xenograft tumors and metastatic osteosarcoma tumors with no observable toxic effects. Mechanistically, attIL12-PBMC treatment resulted in tumor-restricted antitumor cytokine release and accumulation of attIL12-PBMCs in tumors. It also induced terminal differentiation of osteosarcoma cells into bone-like cells to impede tumor growth.Conclusions
In summary, attIL12-PBMC therapy is safe and effective against osteosarcoma. Our goal is to move this treatment into a clinical trial. Owing to the convenience of the attIL12-PBMC production process, we believe it will be feasible.
SUBMITTER: Yang Q
PROVIDER: S-EPMC10142228 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Yang Qing Q Hu Jiemiao J Jia Zhiliang Z Wang Qi Q Wang Jing J Dao Long Hoang LH Zhang Wendong W Zhang Sheng S Xia Xueqing X Gorlick Richard R Li Shulin S
Clinical cancer research : an official journal of the American Association for Cancer Research 20220901 17
<h4>Purpose</h4>Chimeric antigen receptor (CAR) T-cell therapy has shown great promise for treating hematologic malignancies but requires a long duration of T-cell expansion, is associated with severe toxicity, and has limited efficacy for treating solid tumors. We designed experiments to address those challenges.<h4>Experimental design</h4>We generated a cell membrane-anchored and tumor-targeted IL12 (attIL12) to arm peripheral blood mononuclear cells (PBMC) instead of T cells to omit the expan ...[more]