Research article summary (published 30 Aug 2009):

Brain tumor immunotherapy with type-1 polarizing strategies.

Full Abstract

Although the safety of vaccine approaches for central nervous system (CNS) malignancies has been established in early phase clinical trials, the success of a vaccine strategy will depend critically on the ability of effector T cells to home in to CNS tumors and durably exert antitumor effects. Based on our recent studies, efficient CNS tumor homing is a characteristic of cytotoxic T lymphocytes (CTLs) with a type 1 phenotype (Tc1), and this appears to be related to the Tc1 response to the type 1 CXC chemokine ligand (CXCL) 10 [also known as interferon (IFN)-inducible protein (IP)-10] and expression of an integrin receptor very late antigen (VLA)-4 on Tc1. In addition, we have previously shown that direct intratumoral delivery of dendritic cells (DCs) ex vivo engineered to secrete IFN-alpha further enhances Tc1 homing via upregulation of CXCL10/IP-10 in the tumor microenvironment. As a means to induce IFN-alpha and CXCL10/IP-10 in the CNS tumor microenvironment in a clinically feasible manner, we used administration of polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose (poly-ICLC), a ligand for toll-like receptor 3 and melanoma differentiation-associated gene 5 (MDA5) in combination with vaccinations targeting CTL epitopes derived from glioma-associated antigens (GAAs). The combination of subcutaneous vaccination and i.m. poly-ICLC administration remarkably promoted systemic induction of antigen GAA-specific Tc1s expressing VLA-4 in the CNS tumors and improved the survival of tumor-bearing mice in the absence of detectable autoimmunity. Based on these data, we have implemented a phase I/II vaccination study using type 1 polarizing DCs loaded with GAA peptides in combination with poly-ICLC in patients with recurrent malignant glioma.

Author information

Author/s: Okada, Hideho (H);

Affiliation: University of Pittsburgh School of Medicine, Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. okadah(-atsign-)upmc.edu

Journal and publication information

Publication Type: Journal Article; Review

Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci), published in United States. (Language: eng)

Reference: 2009-Sep; vol 1174 (issue ) : pp 18-23

Dates: Created 2009/09/22; Completed 2009/10/23;

PMID: 19769732, status: MEDLINE (last retrieval date: 10/23/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Brain Neoplasms - immunology Cancer Vaccines - therapeutic use Carboxymethylcellulose - analogs & derivatives; therapeutic use Disease Models, Animal Glioma - immunology Humans Immunotherapy - methods

Mice Poly I-C - therapeutic use Polylysine - analogs & derivatives; therapeutic use RNA, Double-Stranded - immunology RNA, Viral - immunology T-Lymphocytes - immunology T-Lymphocytes, Cytotoxic - immunology Toll-Like Receptor 3 - immunology

Associated Chemicals: Cancer Vaccines (0) ; RNA, Double-Stranded (0) ; RNA, Viral (0) ; TLR3 protein, human (0) ; Toll-Like Receptor 3 (0) ; Poly I-C (24939-03-5) ; Polylysine (25104-18-1) ; poly ICLC (59789-29-6) ; Carboxymethylcellulose (9004-32-4)

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