Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Special Article
  • Published:

Anti-GD2 immunoliposomes loaded with oxamate for neuroblastoma

Pediatric Research volume 94, pages 458–461 (2023)Cite this article

A Correction to this article was published on 17 March 2023

This article has been updated

Abstract

Oncometabolism can be targeted for the development of less myelotoxic oncotherapeutics. Lactate dehydrogenase A (LDHA) is central to the Warburg effect, a potential oncometabolic shift in neuroblastoma (NBL). Advanced surgical, cytotoxic and cell-differentiating therapies improved survival of children with NBL. Anti-GD2 monoclonal antibodies (mAb) effectively targeting NBL are also incorporated into complex therapies. However, poor clinical outcomes of high-risk NBL require improvements. Here, we verified the pre-reported prognostic value of LDHA expression in NBL using the R2 onco-genomics platform. Kaplan–Meier curves re-demonstrated that higher tumor LDHA expression correlates with worse survival. Multivariate statistics confirmed LDHA is independent from age, stage, and MYCN amplification. In conclusion, a molecular construct is proposed with anti-GD2 mAbs utilized for the targeted delivery of liposomes containing an LDHA inhibitor, Oxamate. Development and preclinical testing of this immunoliposome may validate targeted inhibition of the Warburg effect for NBL.

Impact

  • Development of therapeutics against oncometabolism.

  • Targeted specified drug-delivery with mAb.

  • Sparing normal tissues from profound LDHA inhibition.

  • Immunoliposome loaded with an anti-metabolite.

  • If preclinically successful, has translational potential.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Event-free and overall survivals based on tumor LDHA expression.
Fig. 2: Mechanism of action for the proposed immunoliposome.

Similar content being viewed by others

Data availability

The datasets for analyses and generations of Kaplan–Meier plots in this study are available in the R2 Genomics Analysis and Visualization Platform, http://r2.amc.nl.

Change history

References

  1. Strebhardt, K. & Ullrich, A. Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat. Rev. Cancer 8, 473–480 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Weyandt, J. D., Thompson, C. B., Giaccia, A. J. & Rathmell, W. K. Metabolic alterations in cancer and their potential as therapeutic targets. Am. Soc. Clin. Oncol. Educ. Book. 37, 825–832 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Feng, Y. et al. Lactate dehydrogenase A: a key player in carcinogenesis and potential target in cancer therapy. Cancer Med. 7, 6124–6136 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Altinoz, M. A. & Ozpinar, A. Oxamate targeting aggressive cancers with special emphasis to brain tumors. Biomed. Pharmacother. 147, 1–8 (2022).

    Article  Google Scholar 

  5. Dorneburg, C. et al. LDHA in neuroblastoma is associated with poor outcome and its depletion decreases neuroblastoma growth independent of aerobic glycolysis. Clin. Cancer Res. 24, 5772–5783 (2018).

    Article  CAS  PubMed  Google Scholar 

  6. Chung, C. et al. Neuroblastoma. Pediatr. Blood Cancer 68, S1–S8 (2021).

    Article  Google Scholar 

  7. Chan, G. C. & Chan, C. M. Anti-GD2 directed immunotherapy for high-risk and metastatic neuroblastoma. Biomolecules 12, 358 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tarantino, P. et al. Antibody-drug conjugates: smart chemotherapy delivery across tumor histologies. CA Cancer J. Clin. 72, 165–182 (2022).

    Article  PubMed  Google Scholar 

  9. Panosyan, W., Panosyan, D. & Panosyan, E. Warburg effect and cancer survival. J. Stud. Res. 10, 1–13 (2021).

    Article  Google Scholar 

  10. Tibbetts, R. et al. Anti-disialoganglioside antibody internalization by neuroblastoma cells as a mechanism of immunotherapy resistance. Cancer Immunol. Immunother. 71, 153–164 (2022).

    Article  CAS  PubMed  Google Scholar 

  11. Lajoie, N. The Pharmacological Guide to Metformin. Pharmacology – Research, Safety Testing and Regulation (Nova Medicine & Health, New York, 2020).

  12. Qiao, T. et al. Inhibition of LDH-A by oxamate enhances the efficacy of anti-PD-1 treatment in an NSCLC humanized mouse model. Front Oncol. 11, 632364 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Matsuda, Y. & Mendelsohn, B. A. Recent advances in drug-antibody ratio determination of antibody-drug conjugates. Chem. Pharm. Bull. (Tokyo) 69, 976–983 (2021).

    Article  CAS  PubMed  Google Scholar 

  14. Le, N. T. T. et al. Soy lecithin-derived liposomal delivery systems: surface modification and current applications. Int. J. Mol. Sci. 20, 4706 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kasenda, B. et al. Targeting immunoliposomes to EGFR-positive glioblastoma. ESMO Open 7, 100365 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Manuscript review and constructive criticism by Dr Araz Marachelian (Children’s Hospital Los Angeles), and Dr Clarke Anderson (City of Hope, Duarte, California) are highly appreciated.

Author information

Author notes

  1. These authors contributed equally: William S. Panosyan, Daniel E. Panosyan.

Authors and Affiliations

  1. Crescenta Valley High School, La Crescenta, CA, USA

    William S. Panosyan

  2. University of California Los Angeles, College of Letters and Science, Los Angeles, CA, USA

    Daniel E. Panosyan

  3. Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands

    Jan Koster

  4. Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA

    Eduard H. Panosyan

  5. The Lundquist Institute, Torrance, CA, USA

    Eduard H. Panosyan

Authors
  1. William S. Panosyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel E. Panosyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Koster
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eduard H. Panosyan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors made manuscript preparation contributions including conceptual design, analysis, writing, artwork, literature review, and approval of this publication.

Corresponding author

Correspondence to Eduard H. Panosyan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised: due to a publisherĘĽs error, the uncorrected proof PDF of this article was unfortunately published by mistake and has now been replaced by the correct version.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Panosyan, W.S., Panosyan, D.E., Koster, J. et al. Anti-GD2 immunoliposomes loaded with oxamate for neuroblastoma. Pediatr Res 94, 458–461 (2023). https://doi.org/10.1038/s41390-023-02479-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02479-4

Search

Advanced search

Quick links