Year: 2012
Type: article
Study design: Clinical Trial
Abstract: Diffuse brainstem gliomas (BSG), other malignant astrocytomas, and multiply recurrent low-grade gliomas carry a poor prognosis, and new therapies are needed.Having gained experience with immunotherapy for adult gliomas, we extended these insights to childhood gliomas on the basis of our observations regarding their profiles of glioma-associated antigen (GAA) expression.We initiated a pilot trial of subcutaneous vaccinations with peptides for GAA epitopes emulsified in montanide-ISA-51 given every 3 weeks for 8 courses along with intramuscular injections of poly-ICLC in HLA-A2+ children with newly diagnosed BSG, high-grade gliomas (HGG), or recurrent gliomas.The assessed GAAs were EphA2, IL13Ra2, and survivin.Primary endpoints were safety and T cell responses against vaccine-targeted GAAs, assessed by ELISPOT analysis.Treatment response was evaluated clinically and by MR imaging.To date, 28 children have been enrolled, 16 with newly diagnosed BSG, 5 with newly diagnosed HGG, 4 with recurrent low-grade gliomas, and 3 with recurrent HGGs.No dose-limiting non-central nervous system toxicity has been encountered.One child with a BSG had transient tumor enlargement in association with acute neurological deterioration 4 months after beginning vaccination, but that later regressed and culminated in a sustained partial response (PR), consistent with pseudoprogression.Two other children with BSG had symptomatic pseudoprogression, with transient neurological deterioration and tumor enlargement followed by stabilization.Among 24 patients evaluable for response, 3 had rapidly progressive disease, 16 had stable disease for . 2 cycles, 3 had PRs, 1 had a molecular response, and 1 had prolonged diseasefree status after surgery.ELISPOT analyses, completed in 13 children, showed GAA responses in 11, most commonly to IL13Ra2.We conclude that peptide vaccination in children with gliomas is generally well tolerated, although distinguishing pseudoprogression from true progression can be challenging.Immunological and clinical responses have been obtained.More extensive analyses of efficacy in a multi-institutional context are warranted.
Source: Neuro-Oncology
Authors: I. F. Pollack, R. I. Jakacki, L. Butterfield, H. Okada, Y. Chiba, N. Hashimoto, N. Kagawa, M. Kinoshita, N. Kijima, R. Hirayama, Y. Oji, A. Tsuboi, Y. Oka, H. Sugiyama, T. Yoshimine, R. D. Valle, S. Tejada, S. Inoges, M. A. Idoate, A. L. D. de Cerio, J. Espinos, J. Aristu, J. Gallego, J. P. Calvo, M. Bendandi, J. Zhu, C. Chen, A. Ravelo, E. Yu, R. Dhanda, I. D. Schnadig, L. Zhang, H. Fan, I. Zhang, X. Chen, H. Wang, A. Da Fonseca, B. Badie, H. Okada, L. H. Butterfield, R. L. Hamilton, A. H. Mintz, J. A. Engh, J. Drappatz, M. O. Lively, M. D. Chan, A. M. Salazar, D. M. Potter, E. G. Shaw, F. S. Lieberman, J. Wei, L.-Y. Kong, F. Wang, S. Xu, T. A. Doucette, S. D. Ferguson, Y. Yang, K. McEnery, K. Jethwa, O. Gjyshi, W. Qiao, F. F. Lang, G. Rao, G. N. Fuller, G. A. Calin, A. B. Heimberger, S. Yang, G. E. Archer, H. Miao, X. Cui, W. Xie, D. Snyder, A. J. Pretorian, A. Dechkovskaia, E. Reap, L. A. S. Perez, P. Norberg, R. Schmittling, D. A. Mitchell, J. H. Sampson, F. Wang, J. Wei, O. Gjyshi, L.-Y. Kong, S. Xu, F. Lang, G. Calin, A. B. Heimberger, S. Xu, J. Wei, L.-Y. Kong, F. Wang, G. Calin, A. B. Heimberger, D. G. Walker, T. Crough, L. Beagley, C. Smith, L. Jones, R. Khanna, N. Hashimoto, A. Tsuboi, Y. Chiba, N. Kijima, Y. Oka, Y. Oji, M. Kinoshita, N. Kagawa, T. Yoshimine, H. Sugiyama, Y. Kanemura, M. Sumida, E. Yoshioka, A. Yamamoto, D. Kanematsu, Y. Matsumoto, H. Fukusumi, A. Takada, M. Nonaka, S. Nakajima, K. Mori, S. Goto, T. Kamigaki, R. Maekawa, T. Shofuda, S. Moriuchi, M. Yamasaki, J. T. Yeung, R. Hamilton, R. Jakacki, H. Okada, I. Pollack, S. Pellegatta, M. Eoli, C. Antozzi, S. Frigerio, M. G. Bruzzone, L. Cuppini, S. Nava, E. Anghileri, G. Cantini, E. Prodi, E. Ciusani, P. Ferroli, M. Saini, G. Broggi, R. Mantegazza, E. A. Parati, G. Finocchiaro, M. Hegde, A. Corder, K. K. Chow, M. Mukherjee, V. S. Brawley, H. E. Heslop, S. Gottschalk, E. Yvon, N. Ahmed, D. M. Gibo, W. Debinski, J. Bonomo, J. Rossmeisl, J. Robertson, P. Dickinson, M. E. Salacz, P. J. Camarata, M. Ots, J. McIntire, D. Lovick, D. A. Mitchell, G. Archer, D. Bigner, H. Friedman, D. Lally-Goss, B. Perry, J. Herndon, S. McGehee, R. McLendon, R. E. Coleman, J. Sampson, M. Hegde, Z. Grada, T. Byrd, D. R. Shaffer, A. Ghazi, V. S. Brawley, A. Corder, K. Schonfeld, G. Dotti, H. Heslop, S. Gottschalk, W. Wels, M. L. Baker, N. Ahmed, J. M. Robbins, P. J. Dickinson, D. York, B. K. Sturges, B. Martin, R. J. Higgins, J. Bringas, K. Bankiewicz, H. E. Gruber, D. J. Jolly, A. Narayana, M. Mathew, R. Kannan, K. Madden, J. Golfinos, E. Parker, P. Ott, A. Pavlick, D. A. Bota, C. Pretto, P. Hantos, F. M. Hofman, T. C. Chen, J. A. Carrillo, V. E. Schijns, A. A. Stathopoulos, R. M. Prins, R. Everson, H. Soto, D. N. Lisiero, E. Young, L. M. Liau, G. E. Archer, W. Xie, P. Norberg, A. Dechkovskaia, A. Friedman, D. D. Bigner, D. A. Mitchell, J. H. Sampson, D. Boczkowski, D. A. Mitchell, S. G. Gururangan, G. Grant, T. Driscoll, G. Archer, J. King, D. Boczkowski, W. Xie, S. Nair, B. Perry, H. Fuchs, J. Kurtzberg, H. Friedman, D. Bigner, J. Sampson, M. A. Shevtsov, A. V. Pozdnyakov, A. V. Kim, K. A. Samochernych, I. V. Guzhova, I. V. Romanova, B. A. Margulis, W. A. Khachatryan
Institutions: Boston Children's Hospital, Children's Hospital of Pittsburgh, Clinica Universidad de Navarra, University of Pittsburgh, UPMC Hillman Cancer Center, Chartered Institute of Management Accountants, The University of Osaka, Universidad de Navarra, Genentech, City Of Hope National Medical Center, Shandong University, Universidade Federal do Rio de Janeiro, Wake Forest University, Duke University, QIMR Berghofer Medical Research Institute, Hyogo Medical University, Baylor College of Medicine, Virginia Tech, University of California, Davis, University of Kansas, Durham University, University of Southern California, Wageningen University & Research, University of California, Irvine, Russian Academy of Sciences, Institute of Evolutionary Physiology and Biochemistry
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2113594104