Top

Published in:

01-12-2022 | Glioblastoma | Research article

Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy

Authors: Justyna Mączyńska, Florian Raes, Chiara Da Pieve, Stephen Turnock, Jessica K. R. Boult, Julia Hoebart, Marcin Niedbala, Simon P. Robinson, Kevin J. Harrington, Wojciech Kaspera, Gabriela Kramer-Marek

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

Surgical resection followed by chemo-radiation postpones glioblastoma (GBM) progression and extends patient survival, but these tumours eventually recur. Multimodal treatment plans combining intraoperative techniques that maximise tumour excision with therapies aiming to remodel the immunologically cold GBM microenvironment could improve patients’ outcomes. Herein, we report that targeted photoimmunotherapy (PIT) not only helps to define tumour location and margins but additionally promotes activation of anti-GBM T cell response.

Methods

EGFR-specific affibody molecule (Z_EGFR:03115) was conjugated to IR700. The response to Z_EGFR:03115-IR700-PIT was investigated in vitro and in vivo in GBM cell lines and xenograft model. To determine the tumour-specific immune response post-PIT, a syngeneic GBM model was used.

Results

In vitro findings confirmed the ability of Z_EGFR:03115-IR700 to produce reactive oxygen species upon light irradiation. Z_EGFR:03115-IR700-PIT promoted immunogenic cell death that triggered the release of damage-associated molecular patterns (DAMPs) (calreticulin, ATP, HSP70/90, and HMGB1) into the medium, leading to dendritic cell maturation. In vivo, therapeutic response to light-activated conjugate was observed in brain tumours as early as 1 h post-irradiation. Staining of the brain sections showed reduced cell proliferation, tumour necrosis, and microhaemorrhage within PIT-treated tumours that corroborated MRI T₂*w acquisitions. Additionally, enhanced immunological response post-PIT resulted in the attraction and activation of T cells in mice bearing murine GBM brain tumours.

Conclusions

Our data underline the potential of Z_EGFR:03115-IR700 to accurately visualise EGFR-positive brain tumours and to destroy tumour cells post-conjugate irradiation turning an immunosuppressive tumour environment into an immune-vulnerable one.

Available only for authorised users

Li CW, Lim SO, Xia W, Lee HH, Chan LC, Kuo CW, et al. Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nat Commun. 2016;7(1):12632. https://doi.org/10.1038/ncomms12632.CrossRefPubMedPubMedCentral

Brown NF, Carter TJ, Ottaviani D, Mulholland P. Harnessing the immune system in glioblastoma. Br J Cancer. 2018;119(10):1171–81. https://doi.org/10.1038/s41416-018-0258-8.CrossRefPubMedPubMedCentral

Binder ZA, Thorne AH, Bakas S, Wileyto EP, Bilello M, Akbari H, et al. Epidermal growth factor receptor extracellular domain mutations in glioblastoma present opportunities for clinical imaging and therapeutic development. Cancer cell. 2018;34(1):163–77 e7. https://doi.org/10.1016/j.ccell.2018.06.006.CrossRefPubMedPubMedCentral

Watts C, Price SJ, Santarius T. Current concepts in the surgical management of glioma patients. Clin Oncol (R Coll Radiol). 2014;26(7):385–94. https://doi.org/10.1016/j.clon.2014.04.001.CrossRef

Majchrzak K, Kaspera W, Bobek-Billewicz B, Hebda A, Stasik-Pres G, Majchrzak H, et al. The assessment of prognostic factors in surgical treatment of low-grade gliomas: a prospective study. Clin Neurol Neurosurg\. 2012;114(8):1135–44. https://doi.org/10.1016/j.clineuro.2012.02.054.CrossRefPubMed

Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462–77. https://doi.org/10.1016/j.cell.2013.09.034.CrossRefPubMedPubMedCentral

Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18(10):1373–85. https://doi.org/10.1016/S1470-2045(17)30517-X.CrossRefPubMed

Concha-Benavente F, Ferris RL. Reversing EGFR mediated immunoescape by targeted monoclonal antibody therapy. Front pharmacol. 2017;8:332. https://doi.org/10.3389/fphar.2017.00332.CrossRefPubMedPubMedCentral

Persico P, Lorenzi E, Dipasquale A, Pessina F, Navarria P, Politi LS, et al. Checkpoint inhibitors as high-grade gliomas treatment: state of the art and future perspectives. J Clin Med. 2021;10(7). https://doi.org/10.3390/jcm10071367.

10.

Jackson CM, Choi J, Lim M. Mechanisms of immunotherapy resistance: lessons from glioblastoma. Nat Immunol. 2019;20(9):1100–9. https://doi.org/10.1038/s41590-019-0433-y.CrossRefPubMed

11.

Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L, Chu T, et al. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. Nat med. 2019;25(3):462–9. https://doi.org/10.1038/s41591-019-0349-y.CrossRefPubMedPubMedCentral

12.

Wang HS, Wan J, Zhou HG, Xu JN, Lu YP, Ji XY, et al. Different T-cell subsets in glioblastoma multiforme and targeted immunotherapy. Cancer Lett. 2021;496:134–43. https://doi.org/10.1016/j.canlet.2020.09.028.CrossRefPubMed

13.

Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li SQ, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019;565(7738):234. https://doi.org/10.1038/s41586-018-0792-9.CrossRefPubMed

14.

Inagaki FF, Furusawa A, Choyke PL, Kobayashi H. Enhanced nanodrug delivery in tumors after near-infrared photoimmunotherapy. Nanophotonics-Berlin. 2019;8(10):1673–88. https://doi.org/10.1515/nanoph-2019-0186.CrossRef

15.

Rajendrakumar SK, Uthaman S, Cho CS, Park IK. Nanoparticle-based phototriggered cancer immunotherapy and its domino effect in the tumor microenvironment. Biomacromolecules. 2018;19(6):1869–87. https://doi.org/10.1021/acs.biomac.8b00460.CrossRefPubMed

16.

Kato T, Okada R, Goto Y, Furusawa A, Inagaki F, Wakiyama H, et al. Electron donors rather than reactive oxygen species needed for therapeutic photochemical reaction of near-infrared photoimmunotherapy. ACS Pharmacol Transl Sci. 2021;4(5):1689–701. https://doi.org/10.1021/acsptsci.1c00184.CrossRefPubMed

17.

Nagaya T, Nakamura Y, Okuyama S, Ogata F, Maruoka Y, Choyke PL, et al. Syngeneic mouse models of oral cancer are effectively targeted by anti-CD44-based NIR-PIT. Mol Cancer Res. 2017;15(12):1667–77. https://doi.org/10.1158/1541-7786.MCR-17-0333.CrossRefPubMedPubMedCentral

18.

Nagaya T, Okuyama S, Ogata F, Maruoka Y, Knapp DW, Karagiannis SN, et al. Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody. Oncotarget. 2018;9(27):19026–38. https://doi.org/10.18632/oncotarget.24876.CrossRefPubMedPubMedCentral

19.

Kato T, Wakiyama H, Furusawa A, Choyke PL, Kobayashi H. Near infrared photoimmunotherapy; a review of targets for cancer therapy. Cancers. 2021;13(11):2535. https://doi.org/10.3390/cancers13112535.CrossRefPubMedPubMedCentral

20.

Wakiyama H, Kato T, Furusawa A, Choyke PL, Kobayashi H. Near infrared photoimmunotherapy of cancer; possible clinical applications. Nanophotonics. 2021;10(12):3135–51. https://doi.org/10.1515/nanoph-2021-0119.CrossRef

21.

Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012;12(12):860–75. https://doi.org/10.1038/nrc3380.CrossRefPubMed

22.

Burley TA, Maczynska J, Shah A, Szopa W, Harrington KJ, Boult JKR, et al. Near-infrared photoimmunotherapy targeting EGFR-shedding new light on glioblastoma treatment. Int J Cancer. 2018;142(11):2363–74. https://doi.org/10.1002/ijc.31246.CrossRefPubMedPubMedCentral

23.

Huang PH, Mukasa A, Bonavia R, Flynn RA, Brewer ZE, Cavenee WK, et al. Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma. Proc Natl Acad Sci USA. 2007;104(31):12867–72. https://doi.org/10.1073/pnas.0705158104.CrossRefPubMedPubMedCentral

24.

Gangoso E, Southgate B, Bradley L, Rus S, Galvez-Cancino F, McGivern N, et al. Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion. Cell. 2021;184(9):2454–2470.e26. https://doi.org/10.1016/j.cell.2021.03.023.CrossRefPubMedPubMedCentral

25.

Burley TA, Da Pieve C, Martins CD, Ciobota DM, Allott L, Oyen WJG, et al. Affibody-based PET imaging to guide EGFR-targeted cancer therapy in head and neck squamous cell cancer models. J Nucl Med. 2019;60(3):353–61. https://doi.org/10.2967/jnumed.118.216069.CrossRefPubMedPubMedCentral

26.

Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, et al. Guidelines for the welfare and use of animals in cancer research. Bri J Cancer. 2010;102(11):1555–77. https://doi.org/10.1038/sj.bjc.6605642.CrossRef

27.

Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412. https://doi.org/10.1371/journal.pbio.1000412.CrossRefPubMedPubMedCentral

28.

Ogawa M, Tomita Y, Nakamura Y, Lee MJ, Lee S, Tomita S, et al. Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity. Oncotarget. 2017;8(6):10425–36. https://doi.org/10.18632/oncotarget.14425.CrossRefPubMedPubMedCentral

29.

Kim JE, Patel MA, Mangraviti A, Kim ES, Theodros D, Velarde E, et al. Combination therapy with anti-PD-1, anti-TIM-3, and focal radiation results in regression of murine gliomas. Clin Cancer Res. 2017;23(1):124–36. https://doi.org/10.1158/1078-0432.Ccr-15-1535.CrossRefPubMed

30.

Chandramohan V, Bao XH, Yu X, Parker S, McDowall C, Yu YR, et al. Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations. J Immunother Cancer. 2019;7. https://doi.org/10.1186/s40425-019-0614-0.

31.

Chen CY, Hutzen B, Wedekind MF, Cripe TP. Oncolytic virus and PD-1/PD-L1 blockade combination therapy. Oncolytic Virother. 2018;7:65–77. https://doi.org/10.2147/Ov.S145532.CrossRefPubMedPubMedCentral

32.

O’Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9(399). https://doi.org/10.1126/scitranslmed.aaa0984.

33.

Kobayashi H, Choyke PL. Near-infrared photoimmunotherapy of cancer. Acc Chem Res. 2019;52(8):2332–9. https://doi.org/10.1021/acs.accounts.9b00273.CrossRefPubMedPubMedCentral

34.

Wang M, Rao J, Wang M, Li X, Liu K, Naylor MF, et al. Cancer photo-immunotherapy: from bench to bedside. Theranostics. 2021;11(5):2218–31. https://doi.org/10.7150/thno.53056.CrossRefPubMedPubMedCentral

35.

van Dongen GA, Visser GW, Vrouenraets MB. Photosensitizer-antibody conjugates for detection and therapy of cancer. Adv Drug Deliv Rev. 2004;56(1):31–52. https://doi.org/10.1016/j.addr.2003.09.003.CrossRefPubMed

36.

van Driel P, Boonstra MC, Slooter MD, Heukers R, Stammes MA, Snoeks TJA, et al. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer. J Control Release. 2016;229:93–105. https://doi.org/10.1016/j.jconrel.2016.03.014.CrossRefPubMedPubMedCentral

37.

Maczynska J, Da Pieve C, Burley TA, Raes F, Shah A, Saczko J, et al. Immunomodulatory activity of IR700-labelled affibody targeting HER2. Cell Death Dis. 2020;11(10):886. https://doi.org/10.1038/s41419-020-03077-6.CrossRefPubMedPubMedCentral

38.

Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM, et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol. 2015;6:588. https://doi.org/10.3389/fimmu.2015.00588.CrossRefPubMedPubMedCentral

39.

Alzeibak R, Mishchenko TA, Shilyagina NY, Balalaeva IV, Vedunova MV, Krysko DV. Targeting immunogenic cancer cell death by photodynamic therapy: past, present and future. J Immunother Cancer. 2021;9(1). https://doi.org/10.1136/jitc-2020-001926.

40.

Arvanitis CD, Ferraro GB, Jain RK. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2020;20(1):26–41. https://doi.org/10.1038/s41568-019-0205-x.CrossRefPubMed

41.

Kishimoto S, Oshima N, Yamamoto K, Munasinghe J, Ardenkjaer-Larsen JH, Mitchell JB, et al. Molecular imaging of tumor photoimmunotherapy: evidence of photosensitized tumor necrosis and hemodynamic changes. Free Radic Biol Med. 2018;116:1–10. https://doi.org/10.1016/j.freeradbiomed.2017.12.034.CrossRefPubMed

42.

Nakajima T, Sano K, Mitsunaga M, Choyke PL, Kobayashi H. Real-time monitoring of in vivo acute necrotic cancer cell death induced by near infrared photoimmunotherapy using fluorescence lifetime imaging. Cancer Res. 2012;72(18):4622–8. https://doi.org/10.1158/0008-5472.CAN-12-1298.CrossRefPubMedPubMedCentral

43.

Zhou F, Xing D, Chen WR. Dynamics and mechanism of HSP70 translocation induced by photodynamic therapy treatment. Cancer Lett. 2008;264(1):135–44. https://doi.org/10.1016/j.canlet.2008.01.040.CrossRefPubMed

44.

Panzarini E, Inguscio V, Dini L. Immunogenic cell death: can it be exploited in photodynamic therapy for cancer. Biomed Res Int. 2013;2013:482160. https://doi.org/10.1155/2013/482160.CrossRefPubMed

45.

Tesniere A, Panaretakis T, Kepp O, Apetoh L, Ghiringhelli F, Zitvogel L, et al. Molecular characteristics of immunogenic cancer cell death. Cell Death Differ. 2008;15(1):3–12. https://doi.org/10.1038/sj.cdd.4402269.CrossRefPubMed

46.

Wang XJ, Ji J, Zhang HY, Fan ZX, Zhang LL, Shi L, et al. Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells. Oncotarget. 2015;6(42):44688–702. https://doi.org/10.18632/oncotarget.5975.CrossRefPubMedPubMedCentral

47.

Korbelik M, Sun J, Cecic I. Photodynamic therapy-induced cell surface expression and release of heat shock proteins: relevance for tumor response. Cancer Res. 2005;65(3):1018–26.PubMed

48.

Kleinovink JW, Fransen MF, Lowik CW, Ossendorp F. Photodynamic-immune checkpoint therapy eradicates local and distant tumors by CD8(+) T cells. Cancer Immunol Res. 2017;5(10):832–8. https://doi.org/10.1158/2326-6066.CIR-17-0055.CrossRefPubMed

49.

Schipmann S, Muther M, Stogbauer L, Zimmer S, Brokinkel B, Holling M, et al. Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control. J Neurosurg. 2020;134(2):1–11. https://doi.org/10.3171/2019.11.JNS192443.CrossRef

Title: Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy
Authors: Justyna Mączyńska
Florian Raes
Chiara Da Pieve
Stephen Turnock
Jessica K. R. Boult
Julia Hoebart
Marcin Niedbala
Simon P. Robinson
Kevin J. Harrington
Wojciech Kaspera
Gabriela Kramer-Marek
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Glioblastoma
Glioblastoma
Glioblastoma
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-021-02213-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2022

Systematic analysis of IL-6 as a predictive biomarker and desensitizer of immunotherapy responses in patients with non-small cell lung cancer

Plasma metabolomic profiling of dietary patterns associated with glucose metabolism status: The Maastricht Study

Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial

Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses

Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment

The accuracy of pulse oximetry in measuring oxygen saturation by levels of skin pigmentation: a systematic review and meta-analysis