Tipping a favorable CNS intratumoral immune response using immune stimulation combined with inhibition of tumor-mediated immune suppression

Ling Yuan Kong, Jun Wei, Gregory N. Fuller, Brett Schrand, Konrad Gabrusiewicz, Shouhao Zhou, Ganesh Rao, George Calin, Eli Gilboa, Amy B. Heimberger

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

High-grade gliomas are notoriously heterogeneous regarding antigen expression, effector responses, and immunosuppressive mechanisms. Therefore, combinational immune therapeutic approaches are more likely to impact a greater number of patients and result in longer, durable responses. We have previously demonstrated the monotherapeutic effects of miR-124, which inhibits the signal transducer and activator of transcription 3 (STAT3) immune suppressive pathway, and immune stimulatory 4–1BB aptamers against a variety of malignancies, including genetically engineered immune competent high-grade gliomas. To evaluate potential synergy, we tested an immune stimulatory aptamer together with microRNA-124 (miRNA-124), which blocks tumor-mediated immune suppression, and found survival to be markedly enhanced, including beyond that produced by monotherapy. The synergistic activity appeared to be not only secondary to enhanced CD3+ cell numbers but also to reduced macrophage immune tumor trafficking, indicating that a greater therapeutic benefit can be achieved with approaches that both induce immune activation and inhibit tumor-mediated immune suppression within the central nervous system (CNS) tumors.

Original languageEnglish (US)
Article numbere1117739
JournalOncoImmunology
Volume5
Issue number5
DOIs
StatePublished - May 3 2016

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology

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    Kong, L. Y., Wei, J., Fuller, G. N., Schrand, B., Gabrusiewicz, K., Zhou, S., Rao, G., Calin, G., Gilboa, E., & Heimberger, A. B. (2016). Tipping a favorable CNS intratumoral immune response using immune stimulation combined with inhibition of tumor-mediated immune suppression. OncoImmunology, 5(5), [e1117739]. https://doi.org/10.1080/2162402X.2015.1117739