Immu-04. Rna-engineered T Cells as a Biological Carrier to Deliver Macromolecules to Intracranial Tumors
Year: 2018
Type: conference-abstract
Abstract: With the presence of the blood-brain barrier (BBB), successful immunotherapeutic drug delivery to brain tumors remains a challenge. Immunomodulatory agents such as cytokines can reprogram the intratumoral microenvironment into an activated state; however, systemic cytokine delivery has limited access to the central nervous system (CNS). To overcome the limitations of systemically administered cytokines, we investigated if RNA-engineered T cells could deliver granulocyte macrophage colony stimulating factor (GM-CSF) directly to intracranial tumor. The ability of T cells to cross the BBB and mediate direct cytotoxic killing of brain tumor cells make them an attractive platform for exogenous drug delivery. Using T cell mRNA electroporation, we evaluated GM-CSF secretion and the function of the GM-CSF RNA-engineered T cells. Activated T cells can be modified to secrete GM-CSF protein in vitro, while retaining their inherent effector functions. GM-CSF RNA-engineered T cells effectively delivered GM-CSF to brain tumors in vivo, and significantly prolonged overall survival in a mouse brain tumor model. Importantly, GM-CSF RNA-engineered T cells demonstrated a superior anti-tumor efficacy as relative to unmodified T cells and T cells delivery with systemic administration of GM-CSF. The anti-tumor effects were associated with increased IFNγ levels locally within the tumor microenvironment, and peripherally antigen-specific T cell expansion. These findings demonstrate that RNA-modified T cells may serve as a versatile platform for the effective delivery of biological agents to CNS tumors.
Source: Neuro-Oncology
Authors: Fernanda Guimaraes, Catherine Flores, Changlin Yang, Jeffrey Drake, Elias Sayour, Jianping Huang, Duane Mitchell
Institution: University of Florida
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2809433432