National Brain Tumor Society

July 2009

In this edition:

NBTS Launches New Online Resource Directory
Bevacizumab For Recurrent Alkylator-Refractory Anaplastic Oligodendroglioma
Molecular Properties of CD133+ Glioblastoma Stem Cells Derived From Treatment-Refractory Recurrent Brain Tumors
Antigen-Specific T Cell Response from Dendritic Cell Vaccination Using Cancer Stem-like Cell-Associated Antigens

1. NBTS Launches Online Resource Directory for Your Patients and Their Loved Ones

The Resource Directory is for brain tumor patients, caregivers, and health professionals seeking resources and services for people coping with a brain tumor diagnosis. You can search for resources regarding caregiver support, financial assistance, rehabilitation, and many more.

Search for a resource in the online Resource Directory

2. Bevacizumab For Recurrent Alkylator-Refractory Anaplastic Oligodendroglioma
Marc C. Chamberlain, MD, Sandra Johnston, PhD, RN

A retrospective evaluation of single agent bevacizumab was carried out in adults with recurrent alkylator-refractory 1p19q codeleted anaplastic oligodendrogliomas (AO) with an objective of determining progression-free survival (PFS). There is no standard therapy for alkylator-resistant AO, and hence a need exists for new therapies.

Twenty-two patients aged 24 to 60 years with recurrent AO were treated. All patients had previously been treated with surgery, radiotherapy, adjuvant chemotherapy (temozolomide, 17; carmustine wafers, 4; carmustine, 1), and 1 salvage regimen (procarbazine, lomustine, and vincristine, 15; temozolomide, 6; carmustine wafers, 1). Eleven patients underwent repeat surgery. Patients were treated at second recurrence with bevacizumab, once every 2 weeks, defined as a single cycle. Neurological evaluation was performed every 2 weeks, and neuroradiographic assessment was made after the initial 2 cycles of bevacizumab and subsequently after every 4 cycles of bevacizumab.

A total of 391 cycles of bevacizumab (median, 14.5 cycles; range, 2-39 cycles) were administered. Bevacizumab-related toxicity included fatigue (14 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (5; 1 grade 3), deep vein thrombosis (4; 1 grade 3), and wound dehiscence (2; 1 grade 3). Fifteen (68%) patients demonstrated a partial radiographic response, 1 (5.0%) demonstrated stable disease, and 6 (27%) demonstrated progressive disease after 2 cycles of bevacizumab. Time to tumor progression ranged from 1 to 18 months (median, 6.75 months). Survival ranged from 3 to 19 months (median, 8.5 months). Six-month and 12-month PFS were 68% and 23%, respectively.

Bevacizumab demonstrated efficacy and acceptable toxicity in this cohort of adults with recurrent 1p19q codeleted alkylator-refractory AO.

Article and more information

Source information:
Cancer Cytopathology CA: A Cancer Journal for Clinicians, Volume 115 Issue 8, Pages 1734 1743, Published Online: 5 Feb 2009, Copyright © 2009 American Cancer Society

3. Molecular Properties of CD133+ Glioblastoma Stem Cells Derived From Treatment-Refractory Recurrent Brain Tumors
Umar Akbar, Terreia Jones, John Winestone, Madison Michael, Atul Shukla, Yichun Sun and Christopher Duntsch

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres.

Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype.

These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight.

Article and more information

Source information:
Journal of Neuro-Oncology, Publisher Springer Netherlands, ISSN 0167-594X (Print) 1573-7373 (Online), Issue Volume 94, Number 1 / August, 2009, Category Priority Report, DOI 10.1007/s11060-009-9919-z

4. Antigen-Specific T Cell Response from Dendritic Cell Vaccination Using Cancer Stem-like Cell-Associated Antigens
Qijin Xu, PhD, Gentao Liu, Ph.D., Xiangpeng Yuan, MD, Minlin Xu, MD, Hongqiang Wang, Jianfei Ji, PhD, Bindu Konda, Keith L. Black, MD, John S. Yu, MD

Glioblastoma multiforme is the most aggressive primary brain tumor, with current treatment remaining palliative. Immunotherapies harness the body's own immune system to target cancers and could overcome the limitations of conventional treatments. One active immunotherapy strategy uses dendritic cell (DC)-based vaccination to initiate T cell-mediated anti-tumor immunity. It has been proposed that cancer stem-like cells (CSCs) may play a key role in cancer initiation, progression and resistance to current treatments.

However, whether using human CSC antigens may improve the anti-tumor effect of DC vaccination against human cancer is unclear. In this study, we explored the suitability of CSCs as sources of antigens for DC vaccination again human GBM, with the aim of achieving CSC-targeting and enhanced anti-tumor immunity. We found that CSCs express high levels of tumor associated antigens (TAAs) as well as major histocompatibility complex (MHC) molecules. Furthermore, DC vaccination using CSC antigens elicited antigen-specific T cell responses against CSCs.

DC vaccination induced interferon (IFN) - production is positively correlated with the number of antigen-specific T cells generated. Finally, using a 9L CSC brain tumor model, we demonstrate that vaccination with DCs loaded with 9L CSCs, but not daughter cells or conventionally cultured 9L cells, induced CTLs against CSCs, and prolonged survival in animals bearing 9L CSC tumors. Understanding how immunization with CSCs generates superior anti-tumor immunity may accelerate development of CSC-specific immunotherapies and cancer vaccines.

Article and more information

National Brain Tumor Society is a nonprofit organization inspiring hope and providing leadership within the brain tumor community. We exist to find a cure and improve the quality of life for those affected by brain tumors. We fund strategic research, deliver support services, and promote collaboration.

Patient Services 800 934 2873 | Toll-free 800 770 8287
info@braintumor.org | www.braintumor.org
Update your email preferences or unsubscribe