Induction of robust type-I CD8+ T-cell responses in WHO grade 2 low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC.

Abstract

PURPOSE:

WHO grade 2 low-grade gliomas (LGG) with high risk factors for recurrence are mostly lethal despite current treatments. We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes in HLA-A2(+) adults with high-risk LGGs in the following three cohorts: (i) patients without prior progression, chemotherapy, or radiotherapy (RT); (ii) patients without prior progression or chemotherapy but with prior RT; and (iii) recurrent patients.

EXPERIMENTAL DESIGN:

GAAs were IL13Rα2, EphA2, WT1, and Survivin. Synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for eight courses with intramuscular injections of poly-ICLC, followed by q12 week booster vaccines.

RESULTS:

Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity was encountered except for one case with grade 3 fever, fatigue, and mood disturbance (cohort 1). ELISPOT assays demonstrated robust IFNγ responses against at least three of the four GAA epitopes in 10 and 4 cases of cohorts 1 and 3, respectively. Cohort 1 patients demonstrated significantly higher IFNγ responses than cohort 3 patients. Median progression-free survival (PFS) periods since the first vaccine are 17 months in cohort 1 (range, 10-47+) and 12 months in cohort 3 (range, 3-41+). The only patient with large astrocytoma in cohort 2 has been progression-free for more than 67 months since diagnosis.

CONCLUSION:

The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade 2 glioma patients. These results warrant further evaluations of this approach. Clin Cancer Res; 21(2); 286-94. ©2014 AACR.

• Authors: Hideho Okada, Lisa H Butterfield, Ronald L Hamilton, Aki Hoji, Masashi Sakaki, Brian J Ahn, Gary Kohanbash, Jan Drappatz, Johnathan Engh, Nduka Amankulor, Mark O Lively, Michael D Chan, Andres M Salazar, Edward G Shaw, Douglas M Potter, Frank S Lieberman
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 21 Issue 2 Pg. 286-94 (Jan 15 2015) ISSN: 1557-3265 [Electronic] United States
• PMID: 25424847 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Vaccines, Subunit
• Polylysine
• poly ICLC
• Carboxymethylcellulose Sodium
• Poly I-C

Topics

• Adult
• Antigens, Neoplasm (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Cancer Vaccines (administration & dosage)
• Carboxymethylcellulose Sodium (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Female
• Glioma (drug therapy, immunology, mortality, pathology)
• Humans
• Male
• Middle Aged
• Neoplasm Grading
• Pilot Projects
• Poly I-C (administration & dosage)
• Polylysine (administration & dosage, analogs & derivatives)
• Treatment Outcome
• Vaccines, Subunit (administration & dosage)