New vaccine trial opens for people with low grade astrocytoma and oligodendrogliomas
Posted on: 01/15/2009
Novel peptide-based vaccines for patients with low grade astrocytoma and oligoastrocytoma
Hideho Okada, M.D., Ph.D. University of Pittsburgh Cancer Institute (UPCI)
Gliomas are the most common type of primary brain tumors that grow invasively to the surrounding normal brain. Low-grade astrocytoma and oligoastrocytoma (World Health Organization [WHO] Grade II) are slow-growing glioma with an intrinsic tendency to progress to aggressive malignant glioma. Even though these tumors are not very common, the median survival time is approximately 6-7 years, and most patients eventually decease of malignant transformation of the tumor. There are no standard radiation or chemotherapy regimens that can improve the survival and quality of life of these patients. In contrast to malignant astrocytomas, therapeutic trials have not often addressed the outcome of patients with low-grade astrocytoma, since long-term observation/treatment period that is necessary to evaluate therapeutic benefit may have posed a difficulty to obtain funding support for studies in these subjects.
We have been dedicated to the development of novel immunotherapy approaches for patients with gliomas. The goal is to improve the ability of the immune system to attack and destroy glioma cells. To this end, we have dedicated our major efforts to identify and characterize the key antigenic components (epitope peptides) in proteins that are commonly produced in glioma cells (glioma-associated antigens; GAAs), thereby allowing us to efficiently and safely direct the induction of cytotoxic T-lymphocytes (CTLs) against glioma cells. In our laboratory, we have also found that co-administration of an immunostimulatory agent (adjuvant) poly-ICLC can remarkably enhance the efficacy of epitope peptide-based vaccines.
In this new clinical trial (UPCI 07-057), we will evaluate whether poly-ICLC-assisted vaccinations with 4GAA-specific epitope peptides can induce CTL responses safely in participants with WHO grade II astrocytoma and oligoastrocytoma with poor prognostic factors.
Eligible patients are age ≥18 year old, human leukocyte antigen (HLA)-A2+ patients with histologically diagnosed supratentorial World Health Organization (WHO) grade II astrocytoma or oligoastrocytoma with “high-risk” factors - defined as: 1) age ≥ 40 with any extent resection; 2) age 18-39 with incomplete resection or 3) the tumor size is ≥ 4 cm. The HLA-A2 status can be tested at the UPCI laboratory using peripheral blood samples of candidate patients. Participating patients may have prior radiation therapy, but prior chemotherapy is not allowed.
Patients will have subcutaneous injections of the vaccine every 3 weeks (Weeks 0, 3, 6, 9, 12, 15, 18, and 21), and poly-ICLC injections intramuscularly on the same day as each vaccine and again 4 days after each vaccine.
We believe these patients are particularly suitable for vaccine therapy because their immune system appears to be relatively well maintained in contrast to patients with malignant glioma, who routinely receive immuno-suppressive chemo-/radiotherapy. In addition, as vaccine treatments have relatively mild toxicity profiles based on previous trials, quality of life is expected to be well maintained in participating patients. Relatively slow-growth of these tumors (relative to malignant glioma) is likely to allow for multiple immunizations that may be necessary to induce potent anti-glioma immune response. Eligible participants will receive the first course of vaccinations every three weeks for eight times. Participants who present specific T-cell response against the vaccinated GAA-epitopes will be eligible for continuous vaccines using GAA-epitope peptide(s) that elicited positive response during the initial course, as long as participants do not demonstrate any major toxicity or tumor progression. The trial is partially funded by the Oligo Fund of the Musella Foundation For Brain Tumor Research & Information, Inc, and is open at the University of Pittsburgh Cancer Institute at present. However, to facilitate the accrual, we plan to open the same vaccine trial in Wake Forest University in a near future.
For information contact:
Hideho Okada M.D., Ph.D.
Associate Professor of Neurological Surgery and Surgery
University of PittsburghSchool of Medicine
University of Pittsburgh Cancer Institute
G12.a Research Pavilion at the HillmanCancerCenter
5117 Centre Ave.Pittsburgh, PA, 15213-1863
Phone: (412) 623-1111 FAX: (412) 623-4747
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