Open AccessIMMU-07. A PHASE I STUDY OF MULTIPLE PEPTIDE TUMOR-ASSOCIATED ANTIGEN VACCINES IN NEWLY DIAGNOSED GLIOBLASTOMA
Author(s) -
Kristen A. Batich,
Gary E. Archer,
Pamela K. Norberg,
David Ashley,
John H. Sampson,
Mustafa Khasraw
Publication year - 2021
Publication title -
neuro-oncology advances
Language(s) - English
Resource type - Journals
ISSN - 2632-2498
DOI - 10.1093/noajnl/vdab112.020
Subject(s) - antigen , epitope , adjuvant , immune system , immunology , peptide vaccine , tumor antigen , vaccination , glioma , priming (agriculture) , cd8 , medicine , cytotoxic t cell , tetanus , t cell , toxoid , immunotherapy , biology , cancer research , in vitro , biochemistry , botany , germination
INTRODUCTION Targeting tumor-associated antigens (TAAs) via peptide vaccination has been tested against malignant glioma with minimal success. Poor responses are attributed to relatively low antigen level expression of the TAA and insufficient CD8+ T cell responses. Including a universal class II epitope that provides CD4+ T cell help towards CD8+ responses has been tested with the immunogenic tetanus toxoid epitope P30, but P30 has been employed as a separate peptide in this regard. The current study will employ targeting of three major glioma TAAs: EphA2, pp65 from Cytomegalovirus, and survivin. The ability to induce more potent TAA-specific immune responses will be tested using two novel strategies: P30-linked TAA peptides and a combinatorial vaccination of the linked peptides (P30-EPS). HYPOTHESES In Evaluation of Tumor Associated P30-Peptide Antigen I (ETAPA-I), P30-EPS is anticipated to have an acceptable toxicity profile. Multi-peptide vaccination is thought to bypass tumor heterogeneity and selection of antigen-negative clones, known as antigen escape. Moreover, the administration of EPS covalently linked to P30 is anticipated to increase the magnitude of antigen-specific immune responses and elicit both CD4- and CD8-mediated immune recognition. TRIAL DESIGN/OBJECTIVES A maximum of 24 patients with newly diagnosed, unmethylated WHO grade IV glioma will be treated. Following resection and standard of care chemoradiation, patients will be vaccinated serially during the priming phase (Day 1-22) and booster phase (Day 84 and 140). All P30-EPS vaccines during priming and boosting phases are co-administered with the adjuvant Hiltonol (Oncovir, poly-ICLC), and patients self-administer Hiltonol throughout the booster phase. The primary endpoint will evaluate the safety profile of P30-EPS. Secondary objectives include polyfunctional T-cell responses specific to EphA2, pp65 and survivin, TCR diversity, and survival. CONCLUSION We describe a study that employs known TAA targets of malignant glioma with the novel strategy of combinatorial class II-linked peptide vaccination.