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)
JournalOncoImmunology
DOIs
StateAccepted/In press - Apr 18 2016

Fingerprint

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

Keywords

  • Aptamer
  • CNS
  • gliomas
  • microRNA
  • STAT3

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

Cite this

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, 18.04.2016.

Research output: Contribution to journalArticle

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.
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