Dendritic Cell Vaccine for Patients With Brain Tumors

Summary

The main purpose of this study is to evaluate the most effective immunotherapy vaccine components in patients with malignant glioma. Teh investigators previous phase I study (IRB #03-04-053) already confirmed that this vaccine procedure is safe in patients with malignant brain tumors, and with an indication of extended survival in several patients. However, the previous trial design did not allow us to test which formulation of the vaccine was the most effective. This phase II study will attempt to dissect out which components are most effective together. Dendritic cells (DC) (cells which "present" or "show" cell identifiers to the immune system) isolated from the subject's own blood will be treated with tumor-cell lysate isolated from tumor tissue taken from the same subject during surgery. This pulsing (combining) of antigen-presenting and tumor lysate will be done to try to stimulate the immune system to recognize and destroy the patient's intracranial brain tumor. These pulsed DCs will then be injected back into the patient intradermally as a vaccine. The investigators will also utilize adjuvant imiquimod or poly ICLC (interstitial Cajal-like cell) in some treatment cohorts. It is thought that the host immune system might be taught to "recognize" the malignant brain tumor cells as "foreign" to the body by effectively presenting unique tumor antigens to the host immune cells (T-cells) in vivo.

Timeline

Start

2010-10-08

Primary completion

2024-08-21

Completion

2024-08-21

Publications

• Background Liau LM, Black KL, Prins RM, Sykes SN, DiPatre PL, Cloughesy TF, Becker DP, Bronstein JM. Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg. 1999 Jun;90(6):1115-24. doi: 10.3171/jns.1999.90.6.1115.
• Background Liau LM, Prins RM, Kiertscher SM, Odesa SK, Kremen TJ, Giovannone AJ, Lin JW, Chute DJ, Mischel PS, Cloughesy TF, Roth MD. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 2005 Aug 1;11(15):5515-25. doi: 10.1158/1078-0432.CCR-05-0464.
• Background Prins RM, Liau LM. Cellular immunity and immunotherapy of brain tumors. Front Biosci. 2004 Sep 1;9:3124-36. doi: 10.2741/1465.
• Background Prins RM, Cloughesy TF, Liau LM. Cytomegalovirus immunity after vaccination with autologous glioblastoma lysate. N Engl J Med. 2008 Jul 31;359(5):539-41. doi: 10.1056/NEJMc0804818. No abstract available.
• Everson RG, Hugo W, Sun L, Antonios J, Lee A, Ding L, Bu M, Khattab S, Chavez C, Billingslea-Yoon E, Salazar A, Ellingson BM, Cloughesy TF, Liau LM, Prins RM. TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial. Nat Commun. 2024 May 8;15(1):3882. doi: 10.1038/s41467-024-48073-y.
• Everson RG, Hugo W, Sun L, Antonios J, Lee A, Ding L, Bu M, Khattab S, Chavez C, Billingslea-Yoon E, Salazar A, Ellingson BM, Cloughesy TF, Liau LM, Prins RM. Dendritic Cell Vaccination in Conjunction with a TLR Agonist Polarizes Interferon Immune Responses in Malignant Glioma Patients. Res Sq [Preprint]. 2023 Sep 12:rs.3.rs-3287211. doi: 10.21203/rs.3.rs-3287211/v1.

Drugs

Indications