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Membrane-Anchored and Tumor-Targeted IL12 (attIL12)-PBMC Therapy for Osteosarcoma.


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

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Publications

Membrane-Anchored and Tumor-Targeted IL12 (attIL12)-PBMC Therapy for Osteosarcoma.

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]

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2021-12-01 | GSE161771 | GEO