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Regular and Young Investigator Award Abstracts
Tumor and Stromal Cell Biology
1368 Characterizing changes in antigen presentation of glioblastoma tumors in response to oncolytic viral therapy
  1. Alicia D’Souza1,
  2. Ryuhjin Ahn1,
  3. GBM TeamLab2 and
  4. Forest White1
  1. 1Massachusetts Institute of Technology, Cambridge, MA, USA
  2. 2Break Through Cancer, Cambridge, MA, USA

  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.

Abstract

Background Glioblastoma (GBM) is a deadly brain cancer with rapid progression and limited treatment options. Numerous clinical trials of immunotherapies have failed to show improvement in patient survival. To develop more effective therapies, understanding the immunopeptidome—the repertoire of peptides presented by major histocompatibility complex (MHC) molecules on tumor cells—is crucial. A better understanding of the antigen landscape of GBM could allow for the development of immunotherapeutic treatment modalities against tumor associated antigens (TAAs) present in GBM.

Methods We used mass spectrometry based immunopeptidomics to characterize the immunopeptidome of serial tumor biopsies from 6 GBM patients treated with up to six intratumoral injections of CAN-3110, an oncolytic viral immunotherapy.1 We also used mass spectrometry to profile changes in protein expression.

Results We show that treatment with CAN-3110 leads to significantly increased HLA Class I and Class II expression in the first two time points (15 and 30 days) after the initiation of therapy. Additionally, we demonstrate that the immunopeptidome of GBM in response to CAN-3110 is highly dynamic, with changes in presentation of specific antigens observed within 15 days. Enrichment analysis on tumor protein expression unveils early increases in proteins associated with an interferon gamma response. At a patient-specific level, we identify biological processes that are enriched in the peptides that are being presented and identify proteins that result in multiple peptides being presented. Some patients also show an increase in peptides that are known cancer testis antigens or predicted tumor-associated antigens.

Conclusions Our results show that we observe dynamic chances in the immunopeptidome in GBM in response to CAN-3110. These results highlight that oncolytic viral immunotherapy may be a promising treatment modality to boost antigen presentation and promote an anti-tumor immune response. Understanding the evolution of the immunopeptidome longitudinally can inform the development of therapeutic agents that target tumor associated antigens.

Acknowledgements This work was supported by the Break Through Cancer foundation.

Reference

  1. Ling AL, Solomon IH, Landivar AM, et al. Clinical trial links oncolytic immunoactivation to survival in glioblastoma. Nature 2023;623:157–166. https://doi.org/10.1038/s41586-023-06623-2.

Ethics Approval The study was approved by DFCI IRB 16-557.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jitc-2024-SITC2024.1368

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