A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Vaccine Therapy Design
2.2. Patient Eligibility
2.3. Peptides
2.4. Vaccine Preparation and Treatment Protocol
2.5. Radiologic Response Monitoring and Other Clinical Endpoints
2.6. Toxicity Assessment
2.7. CTL Responses to Peptide Stimulation
2.8. Statistical Analysis
3. Results
3.1. Demographics and Clinical Characteristics
3.2. Toxicity
3.3. CTL Response
3.4. Clinical Outcomes
3.5. A Case of CR following Peptide Vaccination
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Case No. | Age (Years) | Sex | Diagnosis | Tumor Size (mm) | Operation | Radiotherapy | Chemotherapy | IDH1 Mutation | 1p/19q Codeletion | MGMT Methylation |
---|---|---|---|---|---|---|---|---|---|---|
1 | 17 | M | GB | 32.5 × 29.5 × 32.5 | 2 | 60 Gy | TMZ, ICE | WT | (−) | (−) |
2 | 38 | M | HGG | 20.6 × 11.7 × 16.6 | 0 | 60 Gy + SRT30 Gy | TMZ | NT | NT | NT |
3 | 38 | M | GB with oligo | No enhanced lesion * | 2 | 60 Gy | TMZ | WT | NT | (−) |
4 | 66 | F | GB | 18.0 × 11.5 × 20.0 | 1 | 60 Gy | TMZ, BEV | NT | NT | NT |
5 | 46 | F | sGB | 48.0 × 25.0 × 48.8 | 5 | GK, 60 Gy | TMZ, IFNb, BEV | NT | NT | NT |
6 | 33 | F | AOA | 12.0 × 8.5 × 18.0 | 4 | 60 Gy | TMZ | R132H | (−) | (−) |
7 | 72 | M | OA rec | 33.0 × 20.5 × 23.7 | 1 | 60 Gy | TMZ, BEV | WT | (−) | (±) |
8 | 36 | F | sGB | 16.0 × 13.0 × 18.6 | 2 | 60 Gy | TMZ, BEV | R132H | (−) | (−) |
9 | 27 | F | sGB | 30.2 × 24.1 × 28.6 | 1 | SRT | TMZ, BEV | R132H | (−) | (+) |
10 | 67 | F | GB | 23.3 × 12.1 × 17.5 | 2 | 60 Gy | TMZ | WT | (−) | (±) |
Case No. | Vaccination | LY6K | FOXM1 | DEPDC1 | KIF20A | VEGFR1 | VEGFR2 | Positive Control |
---|---|---|---|---|---|---|---|---|
1 | before | − | + | + | + | + | − | +++ |
2 weeks after | +++ | +++ | +++ | + | + | − | +++ | |
2 | before | − | − | + | + | − | − | +++ |
2 weeks after | +++ | +++ | +++ | + | − | − | +++ | |
3 | before | − | − | NT | NT | − | NT | +++ |
2 weeks after | + | +++ | + | − | + | NT | +++ | |
4 | before | − | + | + | − | − | + | +++ |
2 weeks after | +++ | +++ | +++ | + | − | + | +++ | |
5 | before | − | + | − | − | − | − | +++ |
2 weeks after | +++ | +++ | +++ | + | + | +++ | +++ | |
6 | before | − | + | − | − | − | − | +++ |
2 weeks after | +++ | +++ | +++ | + | + | +++ | +++ |
Case No. | Frequency of Vaccination | Period of Vaccination (mo) | Evaluation after 3 Months | Evaluation after 6 Months | PFS (mo) | OS (mo) |
---|---|---|---|---|---|---|
1 | 18 | 6.2 | PD | PD | 6.3 | 8.9 |
2 | 11 | 6.7 | PD | PD | 6.8 | 18.9 |
3 | 26 | 21.0 | SD | SD | 18.2 | 34.3 |
4 | 12 | 4.8 | PD | PD | 4.9 | 9.1 |
5 | 8 | 1.6 | PD | PD | 1.7 | 8.1 |
6 | 20 | 37.5 | PR | PR * | 38.1 | 38.1 |
7 | 8 | 1.6 | PD | Dead | 1.9 | 3.6 |
8 | 11 | 4.6 | SD | PD | 4.7 | 7.7 |
9 | 10 | 2.1 | PD | PD | 2.9 | 9.4 |
10 | 18 | 10.8 | SD | SD | 11.0 | 23.6 |
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Kikuchi, R.; Ueda, R.; Saito, K.; Shibao, S.; Nagashima, H.; Tamura, R.; Morimoto, Y.; Sasaki, H.; Noji, S.; Kawakami, Y.; et al. A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma. J. Clin. Med. 2019, 8, 263. https://doi.org/10.3390/jcm8020263
Kikuchi R, Ueda R, Saito K, Shibao S, Nagashima H, Tamura R, Morimoto Y, Sasaki H, Noji S, Kawakami Y, et al. A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma. Journal of Clinical Medicine. 2019; 8(2):263. https://doi.org/10.3390/jcm8020263
Chicago/Turabian StyleKikuchi, Ryogo, Ryo Ueda, Katsuya Saito, Shunsuke Shibao, Hideaki Nagashima, Ryota Tamura, Yukina Morimoto, Hikaru Sasaki, Shinobu Noji, Yutaka Kawakami, and et al. 2019. "A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma" Journal of Clinical Medicine 8, no. 2: 263. https://doi.org/10.3390/jcm8020263
APA StyleKikuchi, R., Ueda, R., Saito, K., Shibao, S., Nagashima, H., Tamura, R., Morimoto, Y., Sasaki, H., Noji, S., Kawakami, Y., Yoshida, K., & Toda, M. (2019). A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma. Journal of Clinical Medicine, 8(2), 263. https://doi.org/10.3390/jcm8020263