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 Citations (Scopus)

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

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Central Nervous System
Glioma
Neoplasms
STAT3 Transcription Factor
Central Nervous System Neoplasms
Immunosuppressive Agents
MicroRNAs
Cell Count
Macrophages
Antigens
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Kong, Ling Yuan ; Wei, Jun ; Fuller, Gregory N. ; Schrand, Brett ; Gabrusiewicz, Konrad ; Zhou, Shouhao ; Rao, Ganesh ; Calin, George ; Gilboa, Eli ; Heimberger, Amy B. / Tipping a favorable CNS intratumoral immune response using immune stimulation combined with inhibition of tumor-mediated immune suppression. In: OncoImmunology. 2016 ; Vol. 5, No. 5.
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Kong, LY, Wei, J, Fuller, GN, Schrand, B, Gabrusiewicz, K, Zhou, S, Rao, G, Calin, G, Gilboa, E & Heimberger, AB 2016, 'Tipping a favorable CNS intratumoral immune response using immune stimulation combined with inhibition of tumor-mediated immune suppression', OncoImmunology, vol. 5, no. 5, e1117739. https://doi.org/10.1080/2162402X.2015.1117739

Tipping a favorable CNS intratumoral immune response using immune stimulation combined with inhibition of tumor-mediated immune suppression. / Kong, Ling Yuan; Wei, Jun; Fuller, Gregory N.; Schrand, Brett; Gabrusiewicz, Konrad; Zhou, Shouhao; Rao, Ganesh; Calin, George; Gilboa, Eli; Heimberger, Amy B.

In: OncoImmunology, Vol. 5, No. 5, e1117739, 03.05.2016.

Research output: Contribution to journalArticle

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AU - Zhou, Shouhao

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AU - Calin, George

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