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Abscopal effects of radiotherapy and combined mRNA-based immunotherapy in a syngeneic, OVA-expressing thymoma mouse model

Cancer Immunology, Immunotherapy volume 67, pages 653–662 (2018)Cite this article

Abstract

Background

Tumor metastasis and immune evasion present major challenges of cancer treatment. Radiotherapy can overcome immunosuppressive tumor microenvironments. Anecdotal reports suggest abscopal anti-tumor immune responses. This study assesses abscopal effects of radiotherapy in combination with mRNA-based cancer vaccination (RNActive®).

Methods

C57BL/6 mice were injected with ovalbumin-expressing thymoma cells into the right hind leg (primary tumor) and left flank (secondary tumor) with a delay of 4 days. Primary tumors were irradiated with 3 × 2 Gy, while secondary tumors were shielded. RNA and combined treatment groups received mRNA-based RNActive® vaccination.

Results

Radiotherapy and combined radioimmunotherapy significantly delayed primary tumor growth with a tumor control in 15 and 53% of mice, respectively. In small secondary tumors, radioimmunotherapy significantly slowed growth rate compared to vaccination (p = 0.002) and control groups (p = 0.01). Cytokine microarray analysis of secondary tumors showed changes in the cytokine microenvironment, even in the non-irradiated contralateral tumors after combination treatment.

Conclusion

Combined irradiation and immunotherapy is able to induce abscopal responses, even with low, normofractionated radiation doses. Thus, the combination of mRNA-based vaccination with irradiation might be an effective regimen to induce systemic anti-tumor immunity.

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Abbreviations

BED:

Biologically effective dose

DAMP:

Danger-associated molecular pattern

DC:

Dendritic cell

PGE2:

Prostaglandin E2

s.c.:

Subcutaneously

RT:

Radiotherapy

TAM:

Tumor-associated macrophage

Treg :

Regulatory T

VEGF:

Vascular endothelial growth factor

References

  1. Sporn MB (1996) The war on cancer. Lancet 347:1377–1381

    CAS  Article  PubMed  Google Scholar 

  2. Sporn MB (1997) The war on cancer: a review. Ann N Y Acad Sci 833:137–146

    CAS  Article  PubMed  Google Scholar 

  3. Geiger TR, Peeper DS (2009) Metastasis mechanisms. Biochim Biophys Acta 1796:293–308

    CAS  PubMed  Google Scholar 

  4. Whiteside TL, Demaria S, Rodriguez-Ruiz ME, Zarour HM, Melero I (2016) Emerging opportunities and challenges in cancer immunotherapy. Clin Cancer Res 22:1845–1855

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ et al (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811

    CAS  Article  PubMed  Google Scholar 

  6. Vicari AP, Caux C, Trinchieri G (2002) Tumour escape from immune surveillance through dendritic cell inactivation. Semin Cancer Biol 12:33–42

    CAS  Article  PubMed  Google Scholar 

  7. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S et al (1996) Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2:1096–1103

    CAS  Article  PubMed  Google Scholar 

  8. Kobie JJ, Wu RS, Kurt RA, Lou S, Adelman MK, Whitesell LJ et al (2003) Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res 63:1860–1864

    CAS  PubMed  Google Scholar 

  9. Melief CJ (2008) Cancer immunotherapy by dendritic cells. Immunity 29:372–383

    CAS  Article  PubMed  Google Scholar 

  10. Wang HY, Wang RF (2007) Regulatory T cells and cancer. Curr Opin Immunol 19:217–223

    CAS  Article  PubMed  Google Scholar 

  11. Triozzi PL, Khurram R, Aldrich WA, Walker MJ, Kim JA, Jaynes S (2000) Intratumoral injection of dendritic cells derived in vitro in patients with metastatic cancer. Cancer 89:2646–2654

    CAS  Article  PubMed  Google Scholar 

  12. Yang D, Chen Q, Yang H, Tracey KJ, Bustin M, Oppenheim JJ (2007) High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin. J Leukoc Biol 81:59–66

    CAS  Article  PubMed  Google Scholar 

  13. Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305

    CAS  Article  PubMed  Google Scholar 

  14. Sanchez-Sanchez N, Riol-Blanco L, Rodriguez-Fernandez JL (2006) The multiple personalities of the chemokine receptor CCR7 in dendritic cells. J Immunol 176:5153–5159

    CAS  Article  PubMed  Google Scholar 

  15. Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L et al (2004) Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys 58:862–870

    Article  PubMed  Google Scholar 

  16. Jonathan EC, Bernhard EJ, McKenna WG (1999) How does radiation kill cells? Curr Opin Chem Biol 3:77–83

    CAS  Article  PubMed  Google Scholar 

  17. Matsumoto H, Takahashi T, Mitsuhashi N, Higuch K, Niibe H (1999) Modification of tumor-associated antigen (CEA) expression of human lung cancer cells by irradiation, either alone or in combination with interferon-gamma. Anticancer Res 19:307–311

    CAS  PubMed  Google Scholar 

  18. Hareyama M, Imai K, Kubo K, Takahashi H, Koshiba H, Hinoda Y et al (1991) Effect of radiation on the expression of carcinoembryonic antigen of human gastric adenocarcinoma cells. Cancer 67:2269–2274

    CAS  Article  PubMed  Google Scholar 

  19. Kunala S, Macklis RM (2001) Ionizing radiation induces CD20 surface expression on human B cells. Int J Cancer 96:178–181

    CAS  Article  PubMed  Google Scholar 

  20. Bhattacharyya T, Purushothaman K, Puthiyottil SS, Bhattacharjee A, Muttah G (2016) Immunological interactions in radiotherapy-opening a new window of opportunity. Ann Transl Med 4:51

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chandra RA, Wilhite TJ, Balboni TA, Alexander BM, Spektor A, Ott PA et al (2015) A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology 4:e1046028

    Article  PubMed  PubMed Central  Google Scholar 

  22. Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S et al (2012) Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 366:925–931

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Frey B, Rubner Y, Wunderlich R, Weiss EM, Pockley AG, Fietkau R et al (2012) Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation - implications for cancer therapies. Curr Med Chem 19:1751–1764

    CAS  Article  PubMed  Google Scholar 

  24. Golden EB, Chhabra A, Chachoua A, Adams S, Donach M, Fenton-Kerimian M et al (2015) Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol 16:795–803

    CAS  Article  PubMed  Google Scholar 

  25. Golden EB, Demaria S, Schiff PB, Chachoua A, Formenti SC (2013) An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res 1:365–372

    Article  PubMed  PubMed Central  Google Scholar 

  26. Demaria S, Pilones KA, Vanpouille-Box C, Golden EB, Formenti SC (2014) The optimal partnership of radiation and immunotherapy: from preclinical studies to clinical translation. Radiat Res 182:170–181

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Siva S, MacManus MP, Martin RF, Martin OA (2015) Abscopal effects of radiation therapy: a clinical review for the radiobiologist. Cancer Lett 356:82–90

    CAS  Article  PubMed  Google Scholar 

  28. Grimaldi AM, Simeone E, Giannarelli D, Muto P, Falivene S, Borzillo V et al (2014) Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Oncoimmunology 3:e28780

    Article  PubMed  PubMed Central  Google Scholar 

  29. Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D (2015) The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev 41:503–510

    Article  PubMed  PubMed Central  Google Scholar 

  30. Fotin-Mleczek M, Duchardt KM, Lorenz C, Pfeiffer R, Ojkic-Zrna S, Probst J et al (2011) Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J Immunother 34:1–15

    CAS  Article  PubMed  Google Scholar 

  31. Lorenz C, Fotin-Mleczek M, Roth G, Becker C, Dam TC, Verdurmen WP et al (2011) Protein expression from exogenous mRNA: uptake by receptor-mediated endocytosis and trafficking via the lysosomal pathway. RNA Biol 8:627–636

    CAS  Article  PubMed  Google Scholar 

  32. Formenti SC, Demaria S (2013) Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 105:256–265

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. Fotin-Mleczek M, Zanzinger K, Heidenreich R, Lorenz C, Kowalczyk A, Kallen KJ et al (2014) mRNA-based vaccines synergize with radiation therapy to eradicate established tumors. Radiat Oncol 9:180

    Article  PubMed  PubMed Central  Google Scholar 

  34. Whitney RB, Levy JG, Smith AG (1974) Influence of tumor size and surgical resection on cell-mediated immunity in mice. J Natl Cancer Inst 53:111–116

    CAS  Article  PubMed  Google Scholar 

  35. Ghiringhelli F, Larmonier N, Schmitt E, Parcellier A, Cathelin D, Garrido C et al (2004) CD4 + CD25 + regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 34:336–344

    CAS  Article  PubMed  Google Scholar 

  36. Gulley JL, Madan RA, Schlom J (2011) Impact of tumour volume on the potential efficacy of therapeutic vaccines. Curr Oncol 18:e150–e157

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Richard Wayne Joseph JE-S, Jedd D, Wolchok AM, Joshua A, Ribas F, Anderson KM, Gangadhar TC, Hodi S, Hamid O, Robert C, Daud A, Hwu W-J, Kefford R, Hersey P, Weber JS, Patnaik A, De Alwis DP, Perrone AM, Kang SP, Ebbinghaus S (2014) Baseline tumor size as an independent prognostic factor for overall survival in patients with metastatic melanoma treated with the anti-PD-1 monoclonal antibody MK-3475. J Clin Oncol 32:5 (Abstract)

    Google Scholar 

  38. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC et al (2009) Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res 15:5379–5388

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR et al (2014) Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 124:687–695

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E et al (2015) Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520:373–377

    CAS  Article  PubMed  Google Scholar 

  41. Marconi R, Strolin S, Bossi G, Strigari L (2017) A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger? PLoS One 12:e0171559

    Article  PubMed  PubMed Central  Google Scholar 

  42. Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ et al (2017) DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun 8:15618

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ma S, Kong B, Liu B, Liu X (2013) Biological effects of low-dose radiation from computed tomography scanning. Int J Radiat Biol 89:326–333

    CAS  Article  PubMed  Google Scholar 

  44. Janiak MK, Wincenciak M, Cheda A, Nowosielska EM, Calabrese EJ (2017) Cancer immunotherapy: how low-level ionizing radiation can play a key role. Cancer Immunol Immunother 66:819–932

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. Eckert F, Gaipl US, Niedermann G, Hettich M, Schilbach K, Huber SM et al (2017) Beyond checkpoint inhibition—immunotherapeutical strategies in combination with radiation. Clin Trans Radiat Oncol 2:29–35

    Article  Google Scholar 

  46. Eckert F, Jelas I, Oehme M, Huber SM, Sonntag K, Welker C et al (2017) Tumor-targeted IL-12 combined with local irradiation leads to systemic tumor control via abscopal effects in vivo. Oncoimmunology 6:e1323161

    Article  PubMed  Google Scholar 

  47. Lugade AA, Sorensen EW, Gerber SA, Moran JP, Frelinger JG, Lord EM (2008) Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J Immunol 180:3132–3139

    CAS  Article  PubMed  Google Scholar 

  48. Matsumura S, Wang B, Kawashima N, Braunstein S, Badura M, Cameron TO et al (2008) Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol 181:3099–3107

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. Matsumura S, Demaria S (2010) Up-regulation of the pro-inflammatory chemokine CXCL16 is a common response of tumor cells to ionizing radiation. Radiat Res 173:418–425

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621

    CAS  Article  PubMed  Google Scholar 

  51. Wennerberg E, Lhuillier C, Vanpouille-Box C, Pilones KA, Garcia-Martinez E, Rudqvist NP et al (2017) Barriers to radiation-induced in situ tumor vaccination. Front Immunol 8:229

    Article  PubMed  PubMed Central  Google Scholar 

  52. Vanpouille-Box C, Pilones KA, Wennerberg E, Formenti SC, Demaria S (2015) In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. Vaccine 33:7415–7422

    Article  PubMed  PubMed Central  Google Scholar 

  53. Rodriguez-Ruiz ME, Rodriguez I, Garasa S, Barbes B, Solorzano JL, Perez-Gracia JL et al (2016) Abscopal effects of radiotherapy are enhanced by combined immunostimulatory mAbs and are dependent on CD8 T cells and crosspriming. Cancer Res 76:5994–6005

    CAS  Article  PubMed  Google Scholar 

  54. Yovino S, Kleinberg L, Grossman SA, Narayanan M, Ford E (2013) The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells. Cancer Invest 31:140–144

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. Carl C, Flindt A, Hartmann J, Dahlke M, Rades D, Dunst J et al (2016) Ionizing radiation induces a motile phenotype in human carcinoma cells in vitro through hyperactivation of the TGF-beta signaling pathway. Cell Mol Life Sci 73:427–443

    CAS  Article  PubMed  Google Scholar 

  56. Levy A, Chargari C, Marabelle A, Perfettini JL, Magne N, Deutsch E (2016) Can immunostimulatory agents enhance the abscopal effect of radiotherapy? Eur J Cancer 62:36–45

    CAS  Article  PubMed  Google Scholar 

  57. Schaue D, Comin-Anduix B, Ribas A, Zhang L, Goodglick L, Sayre JW et al (2008) T-cell responses to survivin in cancer patients undergoing radiation therapy. Clin Cancer Res 14:4883–4890

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. Nesslinger NJ, Sahota RA, Stone B, Johnson K, Chima N, King C et al (2007) Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res 13:1493–1502

    CAS  Article  PubMed  Google Scholar 

  59. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD (2016) The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol 13:273–90

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. Farkona S, Diamandis EP, Blasutig IM (2016) Cancer immunotherapy: the beginning of the end of cancer? BMC Med 14:73

    Article  PubMed  PubMed Central  Google Scholar 

  61. Salama AK, Moschos SJ (2017) Next steps in immuno-oncology: enhancing antitumor effects through appropriate patient selection and rationally designed combination strategies. Ann Oncol 28:57–74

    CAS  Article  PubMed  Google Scholar 

  62. Eckert F, Gaipl US, Niedermann G, Hettich M, Schilbach K, Huber SM et al (2017) Beyond checkpoint inhibition—Immunotherapeutical strategies in combination with radiation. Clin Trans Radiat Oncol 2:p29–35

    Article  Google Scholar 

  63. Apetoh L, Ladoire S, Coukos G, Ghiringhelli F (2015) Combining immunotherapy and anticancer agents: the right path to achieve cancer cure? Ann Oncol 26:1813–1823

    CAS  Article  PubMed  Google Scholar 

  64. Sebastian M, Papachristofilou A, Weiss C, Fruh M, Cathomas R, Hilbe W et al (2014) Phase Ib study evaluating a self-adjuvanted mRNA cancer vaccine (RNActive(R)) combined with local radiation as consolidation and maintenance treatment for patients with stage IV non-small cell lung cancer. BMC Cancer 14:748

    Article  PubMed  PubMed Central  Google Scholar 

  65. McNamara MA, Nair SK, Holl EK (2015) RNA-based vaccines in cancer immunotherapy. J Immunol Res 2015:794528

    Article  PubMed  PubMed Central  Google Scholar 

  66. Fiedler K, Lazzaro S, Lutz J, Rauch S, Heidenreich R (2016) mRNA cancer vaccines. Recent Results Cancer Res 209:61–85

    Article  PubMed  Google Scholar 

  67. Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF et al (2016) Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol 17:1497–508

    CAS  Article  PubMed  Google Scholar 

  68. Deplanque G, Shabafrouz K, Obeid M (2017) Can local radiotherapy and IL-12 synergise to overcome the immunosuppressive tumor microenvironment and allow “in situ tumor vaccination”? Cancer Immunol Immunother 66:833–840

    CAS  Article  PubMed  Google Scholar 

  69. Schaue D, Ratikan JA, Iwamoto KS, McBride WH (2012) Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys 83:1306–1310

    CAS  Article  PubMed  Google Scholar 

  70. Demaria S, Formenti SC (2012) Radiation as an immunological adjuvant: current evidence on dose and fractionation. Front Oncol 2:153

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Rodel F, Frey B, Multhoff G, Gaipl U (2015) Contribution of the immune system to bystander and non-targeted effects of ionizing radiation. Cancer Lett 356:105–113

    Article  PubMed  Google Scholar 

  72. Gaipl US, Multhoff G, Scheithauer H, Lauber K, Hehlgans S, Frey B et al (2014) Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy. Immunotherapy 6:597–610

    CAS  Article  PubMed  Google Scholar 

  73. Del Prete G, De Carli M, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S (1993) Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 150:353–360

    PubMed  Google Scholar 

  74. Zlotnik A, Yoshie O (2000) Chemokines: a new classification system and their role in immunity. Immunity 12:121–127

    CAS  Article  PubMed  Google Scholar 

  75. Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172:2731–2738

    CAS  Article  PubMed  Google Scholar 

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Funding

Lucas Basler was funded by a grant of the IZKF Promotionskolleg (Interdisziplinäres Zentrum für Klinische Forschung, Interdisciplinary Centre for Clinical Research, University of Tübingen). Franziska Eckert was partly funded by the Else-Kroener-Fresenius research grant “Therapy resistance of solid tumors” (2015_Kolleg.14).

Author information

Author notes

  1. Lucas Basler

    Present address: Department of Radiation Oncology, University Hospital Zürich, Zurich, Switzerland

  2. Aleksandra Kowalczyk

    Present address: Boehringer-Ingelheim, Birkendorferstr. 85, 88397, Biberach an der Riss, Germany

Affiliations

  1. Department of Radiation Oncology, University of Tübingen, Rämistrasse 100, 8091, Tübingen, Germany

    Lucas Basler, Savas Tsitsekidis, Daniel Zips, Franziska Eckert & Stephan M. Huber

  2. CureVac AG, Tübingen, Germany

    Aleksandra Kowalczyk, Regina Heidenreich & Mariola Fotin-Mleczek

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  1. Lucas Basler
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  2. Aleksandra Kowalczyk
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  4. Mariola Fotin-Mleczek
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  5. Savas Tsitsekidis
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  6. Daniel Zips
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  7. Franziska Eckert
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  8. Stephan M. Huber
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Contributions

LB conducted the experiments and wrote the manuscript. AK helped with the experiments. RH revised the manuscript. MFM helped with the experiments. ST performed the dosimetry experiments. DZ revised the manuscript. FE wrote the manuscript. SMH designed the experiments and revised the manuscript.

Corresponding author

Correspondence to Lucas Basler.

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Conflict of interest

Aleksandra Kowalczyk, Regina Heidenreich, and Mariola Fotin-Mleczek were employees of CureVac AG at the time of the experiments’ performance or preparation of the manuscript. The others authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the animal protection laws and regulations, and were approved by the local authorities.

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Basler, L., Kowalczyk, A., Heidenreich, R. et al. Abscopal effects of radiotherapy and combined mRNA-based immunotherapy in a syngeneic, OVA-expressing thymoma mouse model. Cancer Immunol Immunother 67, 653–662 (2018). https://doi.org/10.1007/s00262-018-2117-0

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Keywords

  • Abscopal effects
  • Immunotherapy
  • Radiotherapy
  • Tumor vaccine
  • Radioimmunotherapy
  • mRNA vaccination