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Li F, Deng L, Jackson KR, et al. Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations. J Immunother Cancer. 2021;9(7)doi: 10.1136/jitc-2021-002531.
Li, F., Deng, L., Jackson, K. R., Talukder, A. H., Katailiha, A. S., Bradley, S. D., Zou, Q., Chen, C., Huo, C., Chiu, Y., Stair, M., Feng, W., Bagaev, A., Kotlov, N., Svekolkin, V., Ataullakhanov, R., Miheecheva, N., Frenkel, F., Wang, Y., Zhang, M., Hawke, D., Han, L., Zhou, S., Zhang, Y., Wang, Z., Decker, W. K., Sonnemann, H. M., Roszik, J., Forget, M. A., Davies, M. A., Bernatchez, C., Yee, C., Bassett, R., Hwu, P., Du, X., & Lizee, G. (2021). Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations. Journal for immunotherapy of cancer, 9(7), . https://doi.org/10.1136/jitc-2021-002531
Li, Fenge, et al. "Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations." Journal for immunotherapy of cancer vol. 9,7 (2021). doi: https://doi.org/10.1136/jitc-2021-002531
Li F, Deng L, Jackson KR, Talukder AH, Katailiha AS, Bradley SD, Zou Q, Chen C, Huo C, Chiu Y, Stair M, Feng W, Bagaev A, Kotlov N, Svekolkin V, Ataullakhanov R, Miheecheva N, Frenkel F, Wang Y, Zhang M, Hawke D, Han L, Zhou S, Zhang Y, Wang Z, Decker WK, Sonnemann HM, Roszik J, Forget MA, Davies MA, Bernatchez C, Yee C, Bassett R, Hwu P, Du X, Lizee G. Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations. J Immunother Cancer. 2021 Jul;9(7). doi: 10.1136/jitc-2021-002531. PMID: 34244308; PMCID: PMC8268925.
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J Immunother Cancer. 2021 Jul;9(7). doi: 10.1136/jitc-2021-002531.

Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations.

Journal for immunotherapy of cancer

Fenge Li, Ligang Deng, Kyle R Jackson, Amjad H Talukder, Arjun S Katailiha, Sherille D Bradley, Qingwei Zou, Caixia Chen, Chong Huo, Yulun Chiu, Matthew Stair, Weihong Feng, Aleksander Bagaev, Nikita Kotlov, Viktor Svekolkin, Ravshan Ataullakhanov, Natalia Miheecheva, Felix Frenkel, Yaling Wang, Minying Zhang, David Hawke, Ling Han, Shuo Zhou, Yan Zhang, Zhenglu Wang, William K Decker, Heather M Sonnemann, Jason Roszik, Marie-Andree Forget, Michael A Davies, Chantale Bernatchez, Cassian Yee, Roland Bassett, Patrick Hwu, Xueming Du, Gregory Lizee

Affiliations

  1. Department of Melanoma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  2. Tianjin HengJia Biotechnology Development Co Ltd, Tianjin, China.
  3. Mary Bird Perkins Cancer Center, Baton Rouge, Louisiana, USA.
  4. Department of Oncology, Tianjin Beichen Hospital, Tianjin, China.
  5. BostonGene Corporation, Waltham, Massachusetts, USA.
  6. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  7. Provincial Clinical College, Fujian Medical University, Fujian, China.
  8. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
  9. Biological Sample Resource Sharing Center, Tianjin First Central Hospital, Tianjin, China.
  10. Department of Immunology, Baylor College of Medicine, Houston, Texas, USA.
  11. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  12. Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
  13. Department of Oncology, Tianjin Beichen Hospital, Tianjin, China [email protected] [email protected].
  14. Department of Melanoma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA [email protected] [email protected].

PMID: 34244308 PMCID: PMC8268925 DOI: 10.1136/jitc-2021-002531

Abstract

BACKGROUND: Neoantigen (NeoAg) peptides displayed at the tumor cell surface by human leukocyte antigen molecules show exquisite tumor specificity and can elicit T cell mediated tumor rejection. However, few NeoAgs are predicted to be shared between patients, and none to date have demonstrated therapeutic value in the context of vaccination.

METHODS: We report here a phase I trial of personalized NeoAg peptide vaccination (PPV) of 24 stage III/IV non-small cell lung cancer (NSCLC) patients who had previously progressed following multiple conventional therapies, including surgery, radiation, chemotherapy, and tyrosine kinase inhibitors (TKIs). Primary endpoints of the trial evaluated feasibility, tolerability, and safety of the personalized vaccination approach, and secondary trial endpoints assessed tumor-specific immune reactivity and clinical responses. Of the 16 patients with epidermal growth factor receptor (EGFR) mutations, nine continued TKI therapy concurrent with PPV and seven patients received PPV alone.

RESULTS: Out of 29 patients enrolled in the trial, 24 were immunized with personalized NeoAg peptides. Aside from transient rash, fatigue and/or fever observed in three patients, no other treatment-related adverse events were observed. Median progression-free survival and overall survival of the 24 vaccinated patients were 6.0 and 8.9 months, respectively. Within 3-4 months following initiation of PPV, seven RECIST-based objective clinical responses including one complete response were observed. Notably, all seven clinical responders had EGFR-mutated tumors, including four patients that had continued TKI therapy concurrently with PPV. Immune monitoring showed that five of the seven responding patients demonstrated vaccine-induced T cell responses against EGFR NeoAg peptides. Furthermore, two highly shared EGFR mutations (L858R and T790M) were shown to be immunogenic in four of the responding patients, all of whom demonstrated increases in peripheral blood neoantigen-specific CD8+ T cell frequencies during the course of PPV.

CONCLUSIONS: These results show that personalized NeoAg vaccination is feasible and safe for advanced-stage NSCLC patients. The clinical and immune responses observed following PPV suggest that EGFR mutations constitute shared, immunogenic neoantigens with promising immunotherapeutic potential for large subsets of NSCLC patients. Furthermore, PPV with concurrent EGFR inhibitor therapy was well tolerated and may have contributed to the induction of PPV-induced T cell responses.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords: EGFR; EGFR inhibitor; neoantigen vaccine; non-small cell lung cancer; tumor regression

Conflict of interest statement

Competing interests: CH and FL are shareholders of Tianjin HengJia Biotechnology Development (‘HengJia Biotech’). GL was a consultant for HengJia Neoantigen Biotechnology (Tianjin), a branch company o

References

  1. Nature. 2013 Jul 11;499(7457):214-218 - PubMed
  2. Cancer Res. 2018 Dec 15;78(24):6728-6735 - PubMed
  3. PLoS One. 2014 Jan 27;9(1):e86655 - PubMed
  4. Target Oncol. 2017 Oct;12(5):563-569 - PubMed
  5. Bioinformatics. 2016 Feb 15;32(4):511-7 - PubMed
  6. J Immunother Cancer. 2019 May 22;7(1):131 - PubMed
  7. BMC Immunol. 2008 Jan 22;9:1 - PubMed
  8. Science. 2015 May 15;348(6236):803-8 - PubMed
  9. IEEE/ACM Trans Comput Biol Bioinform. 2016 May-Jun;13(3):549-56 - PubMed
  10. Cell. 2017 Nov 30;171(6):1259-1271.e11 - PubMed
  11. Science. 2015 Apr 3;348(6230):124-8 - PubMed
  12. Nat Med. 2015 Jan;21(1):12-4 - PubMed
  13. PLoS One. 2016 Jul 28;11(7):e0160004 - PubMed
  14. Nature. 2019 Jan;565(7738):234-239 - PubMed
  15. Oncotarget. 2017 Sep 22;8(52):90557-90578 - PubMed
  16. Adv Immunol. 2007;96:41-101 - PubMed
  17. Nature. 2017 Jul 13;547(7662):217-221 - PubMed
  18. Biochem Biophys Res Commun. 2015 Jul 17-24;463(1-2):95-101 - PubMed
  19. Cancer Res. 2007 Apr 15;67(8):3898-903 - PubMed
  20. Nat Biotechnol. 2016 May;34(5):525-7 - PubMed
  21. J Clin Invest. 2019 Mar 5;129(5):2056-2070 - PubMed
  22. Nature. 2017 Jul 13;547(7662):222-226 - PubMed
  23. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90 - PubMed
  24. Cells. 2018 Nov 15;7(11): - PubMed
  25. Clin Cancer Res. 2018 Dec 15;24(24):6195-6203 - PubMed
  26. Cancer Sci. 2016 Sep;107(9):1179-86 - PubMed
  27. Int J Mol Sci. 2017 Nov 15;18(11): - PubMed
  28. Nature. 2014 Nov 27;515(7528):568-71 - PubMed
  29. Oncoimmunology. 2016 Oct 7;5(12):e1238539 - PubMed
  30. Ann Oncol. 2017 Dec 1;28(suppl_12):xii11-xii17 - PubMed
  31. Science. 2014 May 9;344(6184):641-5 - PubMed
  32. Cancer Discov. 2021 May;11(5):1024-1039 - PubMed
  33. J Immunol. 2013 Aug 15;191(4):1567-77 - PubMed
  34. Nat Med. 2013 Apr;19(4):465-72 - PubMed
  35. Nucleic Acids Res. 2015 Jan;43(Database issue):D784-8 - PubMed
  36. N Engl J Med. 2005 Feb 24;352(8):786-92 - PubMed
  37. Nature. 2019 Jan;565(7738):240-245 - PubMed
  38. Cancer Sci. 2019 Jan;110(1):52-60 - PubMed
  39. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 - PubMed
  40. J Leukoc Biol. 2004 Feb;75(2):163-89 - PubMed
  41. Ann Oncol. 2019 Aug 1;30(8):1311-1320 - PubMed
  42. Nat Genet. 2016 Dec;48(12):1500-1507 - PubMed
  43. J Thorac Oncol. 2015 Jun;10(6):910-23 - PubMed
  44. Front Immunol. 2017 Dec 19;8:1848 - PubMed
  45. Nat Commun. 2018 Jan 2;9(1):20 - PubMed
  46. Immunology. 2018 Jul;154(3):394-406 - PubMed
  47. J Clin Invest. 2019 Mar 1;129(3):1109-1114 - PubMed
  48. Cancer Med. 2019 Apr;8(4):1521-1529 - PubMed
  49. Nature. 2015 Apr 30;520(7549):692-6 - PubMed
  50. F1000Res. 2018 Aug 24;7:1338 - PubMed
  51. Genome Biol. 2016 Jan 26;17:13 - PubMed
  52. Oncotarget. 2016 Aug 23;7(34):54137-54156 - PubMed
  53. CA Cancer J Clin. 2017 Jan;67(1):7-30 - PubMed
  54. Cancers (Basel). 2019 Feb 24;11(2): - PubMed
  55. Cancer Cell. 2019 Jan 14;35(1):10-15 - PubMed
  56. Nature. 2019 Mar;567(7749):479-485 - PubMed
  57. World J Clin Oncol. 2014 Oct 10;5(4):560-7 - PubMed
  58. Oncoimmunology. 2015 Jan 9;4(4):e974411 - PubMed
  59. Semin Immunol. 2016 Feb;28(1):22-7 - PubMed

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