Faculty, Staff and Student Publications
Publication Date
9-1-2022
Journal
Clinical Cancer Research
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.
Keywords
Bone Neoplasms, Cell Line, Tumor, Humans, Immunotherapy, Adoptive, Interleukin-12, Leukocytes, Mononuclear, Osteosarcoma, Receptors, Antigen, T-Cell, Xenograft Model Antitumor Assays
DOI
10.1158/1078-0432.CCR-22-0721
PMID
35727602
PMCID
PMC10142228
PubMedCentral® Posted Date
9-1-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
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