The long-term outcome and efficacy of PR1/BCR-ABL multipeptides vaccination in chronic myeloid leukemia: results of a 7-year longitudinal investigation

Ghaffari, Seyed H.; Osfouri, Ebrahim; Ahmadvand, Mohammad; Bashash, Davood; Ghaffari, Parisa; Niavarani, Ahmadreza; Hossaini, Elham; Yaghmaie, Marjan; Koohi, Roghieh; Ghashgha, Andisheh ie; Pourbagheri-Sigaroodi, Atieh; Mousavi, Seyed A.; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

doi:10.58209/ijbc.14.4.84

Volume 14, Issue 4 ( December 2022 2022) Iranian Journal of Blood and Cancer 2022, 14(4): 84-94 | Back to browse issues page

‎ 10.58209/ijbc.14.4.84

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Ghaffari S H, Osfouri E, Ahmadvand M, Bashash D, Ghaffari P, Niavarani A, et al . The long-term outcome and efficacy of PR1/BCR-ABL multipeptides vaccination in chronic myeloid leukemia: results of a 7-year longitudinal investigation. Iranian Journal of Blood and Cancer 2022; 14 (4) :84-94
URL: http://ijbc.ir/article-1-1354-en.html

The long-term outcome and efficacy of PR1/BCR-ABL multipeptides vaccination in chronic myeloid leukemia: results of a 7-year longitudinal investigation

Seyed H. Ghaffari ^*

¹, Ebrahim Osfouri²

, Mohammad Ahmadvand²

, Davood Bashash³

, Parisa Ghaffari²

, Ahmadreza Niavarani⁴

, Elham Hossaini²

, Marjan Yaghmaie²

, Roghieh Koohi²

, Andisheh ie Ghashgha²

, Atieh Pourbagheri-Sigaroodi⁵

, Seyed A. Mousavi²

, Kamran Alimoghaddam²

, Ardeshir Ghavamzadeh⁶

1- Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran , shghaffari200@yahoo.com
2- Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
3- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
5- Department of Biotechnology, faculty of Advanced Sciences and Technology, Pharmaceutical sciences branch, Islamic Azad University (IAUPS), Tehran, Iran
6- Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, Iran

Abstract: (1073 Views)

Background: Although Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), not all patients reach complete remission and a considerable proportion of the patients develop resistance to Imatinib.
Material and Methods: In an attempt to increase the tail on the survival curve, we conducted a Phase I/II study of PR1/BCR-ABL multipeptides vaccination trial in CML patients with at least 15 months of Imatinib treatment and 5 months of persistent molecular residual disease.
Results: One month after the completion of the vaccinations, 4 patients nearly developed a 1-log fall in their BCR-ABL transcript level, with 4 patients achieving a major molecular response (MMR). Nine patients were followed for more than a period of 7 years. The vaccinations were associated with a MMR in five patients and a complete molecular response (CMR) in one patient. The removal of Imatinib in two patients who achieved MMR after the vaccinations led to a resurgence of the leukemia population and relapse.
Conclusion: Our study suggests that a combination of immunotherapy with Imatinib targeted therapy keeps the leukemia population under control, improving the long-lasting clinical and molecular response of CML patients, for at least 7 years.

Keywords: Multi-peptide vaccination, BCR-ABL, PR1 peptide, Chronic myeloid leukemia

Full-Text [PDF 1738 kb] (679 Downloads)

: Original Article | Subject: Adults Hematology & Oncology
Received: 2022/09/14 | Accepted: 2022/12/22 | Published: 2022/12/28

References

1. [1] Y. Zhou, M.J. You, K.H. Young, P. Lin, G. Lu, L.J. Medeiros, C.E. Bueso-Ramos, Advances in the molecular pathobiology of B-lymphoblastic leukemia, Human pathology, 43 (2012) 1347-1362. [DOI:10.1016/j.humpath.2012.02.004]

2. [2] A. Holleman, M.H. Cheok, M.L. den Boer, W. Yang, A.J. Veerman, K.M. Kazemier, D. Pei, C. Cheng, C.-H. Pui, M.V. Relling, Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment, New England Journal of Medicine, 351 (2004) 533-542. [DOI:10.1056/NEJMoa033513]

3. [3] T. Hughes, M. Deininger, A. Hochhaus, S. Branford, J. Radich, J. Kaeda, M. Baccarani, J. Cortes, N.C. Cross, B.J. Druker, Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results, Blood, 108 (2006) 28-37. [DOI:10.1182/blood-2006-01-0092]

4. [4] S. Abbasian, A. Ghotaslou, A. Ghasemi, F. Nadali, Analysis of expression Of SIRT1 gene in patients with chronic myeloid leukemia resistant to imatinib mesylate, Iranian Journal of Blood and Cancer, 7 (2015) 184-190.

5. [5] J.F. Apperley, Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia, The Lancet. Oncology, 8 (2007) 1018-1029. [DOI:10.1016/S1470-2045(07)70342-X]

6. [6] T. Illmer, M. Schaich, U. Platzbecker, J. Freiberg-Richter, U. Oelschlägel, M. Von Bonin, S. Pursche, T. Bergemann, G. Ehninger, E. Schleyer, P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate, Leukemia, 18 (2004) 401. [DOI:10.1038/sj.leu.2403257]

7. [7] S. Soverini, S. Colarossi, A. Gnani, G. Rosti, F. Castagnetti, A. Poerio, I. Iacobucci, M. Amabile, E. Abruzzese, E. Orlandi, Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia, Clinical Cancer Research, 12 (2006) 7374-7379. [DOI:10.1158/1078-0432.CCR-06-1516]

8. [8] N.P. Shah, J.M. Nicoll, B. Nagar, M.E. Gorre, R.L. Paquette, J. Kuriyan, C.L. Sawyers, Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia, Cancer cell, 2 (2002) 117-125. [DOI:10.1016/S1535-6108(02)00096-X]

9. [9] M. Copland, A. Hamilton, L.J. Elrick, J.W. Baird, E.K. Allan, N. Jordanides, M. Barow, J.C. Mountford, T.L. Holyoake, Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction, Blood, 107 (2006) 4532-4539. [DOI:10.1182/blood-2005-07-2947]

10. [10] J. Ozao-Choy, D.J. Lee, M.B. Faries, Melanoma vaccines: mixed past, promising future, The Surgical clinics of North America, 94 (2014) 1017-1030, viii. [DOI:10.1016/j.suc.2014.07.005]

11. [11] M. Vanneman, G. Dranoff, Combining immunotherapy and targeted therapies in cancer treatment, Nature reviews cancer, 12 (2012) 237. [DOI:10.1038/nrc3237]

12. [12] I. Mellman, G. Coukos, G. Dranoff, Cancer immunotherapy comes of age, Nature, 480 (2011) 480. [DOI:10.1038/nature10673]

13. [13] P.E. Hughes, S. Caenepeel, L.C. Wu, Targeted therapy and checkpoint immunotherapy combinations for the treatment of cancer, Trends in immunology, 37 (2016) 462-476. [DOI:10.1016/j.it.2016.04.010]

14. [14] A.D. Fesnak, C.H. June, B.L. Levine, Engineered T cells: the promise and challenges of cancer immunotherapy, Nature Reviews Cancer, 16 (2016) 566. [DOI:10.1038/nrc.2016.97]

15. [15] H. Wang, F. Cheng, A. Cuenca, P. Horna, Z. Zheng, K. Bhalla, E.M. Sotomayor, Imatinib mesylate (STI-571) enhances antigen-presenting cell function and overcomes tumor-induced CD4+ T-cell tolerance, Blood, 105 (2005) 1135-1143. [DOI:10.1182/blood-2004-01-0027]

16. [16] J. Chen, A. Schmitt, K. Giannopoulos, B. Chen, M. Rojewski, H. Döhner, D. Bunjes, M. Schmitt, Imatinib impairs the proliferation and function of CD4+ CD25+ regulatory T cells in a dose-dependent manner, International journal of oncology, 31 (2007) 1133-1139. [DOI:10.3892/ijo.31.5.1133]

17. [17] T.P. Hughes, J. Kaeda, S. Branford, Z. Rudzki, A. Hochhaus, M.L. Hensley, I. Gathmann, A.E. Bolton, I.C. van Hoomissen, J.M. Goldman, J.P. Radich, S.T.I.S.G. International Randomised Study of Interferon versus, Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia, The New England journal of medicine, 349 (2003) 1423-1432. [DOI:10.1056/NEJMoa030513]

18. [18] B.D. Smith, Y.L. Kasamon, J. Kowalski, C. Gocke, K. Murphy, C.B. Miller, E. Garrett-Mayer, H.L. Tsai, L. Qin, C. Chia, B. Biedrzycki, T.C. Harding, G.H. Tu, R. Jones, K. Hege, H.I. Levitsky, K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate, Clinical cancer research : an official journal of the American Association for Cancer Research, 16 (2010) 338-347. [DOI:10.1158/1078-0432.CCR-09-2046]

19. [19] T. O'Hare, A.S. Corbin, B.J. Druker, Targeted CML therapy: controlling drug resistance, seeking cure, Current opinion in genetics & development, 16 (2006) 92-99. [DOI:10.1016/j.gde.2005.11.002]

20. [20] M. Vakili, S.A. Rasoulinejad, Unusual ophthalmic manifestation in chronic myeloid leukemia: A case report, Iranian Journal of Blood and Cancer, 14 (2022) 58-60.

21. [21] M.W. Deininger, J.M. Goldman, J.V. Melo, The molecular biology of chronic myeloid leukemia, Blood, 96 (2000) 3343-3356. [DOI:10.1182/blood.V96.10.3343.h8003343_3343_3356]

22. [22] P.S. Kim, P.P. Lee, D. Levy, Dynamics and potential impact of the immune response to chronic myelogenous leukemia, PLoS computational biology, 4 (2008) e1000095. [DOI:10.1371/journal.pcbi.1000095]

23. [23] V.P. Balachandran, M.J. Cavnar, S. Zeng, Z.M. Bamboat, L.M. Ocuin, H. Obaid, E.C. Sorenson, R. Popow, C. Ariyan, F. Rossi, P. Besmer, T. Guo, C.R. Antonescu, T. Taguchi, J. Yuan, J.D. Wolchok, J.P. Allison, R.P. DeMatteo, Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido, Nat Med, 17 (2011) 1094-1100. [DOI:10.1038/nm.2438]

24. [24] Q. Ma, C. Wang, D. Jones, K.E. Quintanilla, D. Li, Y. Wang, E.D. Wieder, K. Clise-Dwyer, G. Alatrash, Y. Mj, Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model, Cytotherapy, 12 (2010) 1056-1062. [DOI:10.3109/14653249.2010.506506]

25. [25] K. Rezvani, A.S. Yong, S. Mielke, B.N. Savani, L. Musse, J. Superata, B. Jafarpour, C. Boss, A.J. Barrett, Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies, Blood, 111 (2008) 236-242. [DOI:10.1182/blood-2007-08-108241]

26. [26] N. Jain, J.M. Reuben, H. Kantarjian, C. Li, H. Gao, B.N. Lee, E.N. Cohen, T. Ebarb, D.A. Scheinberg, J. Cortes, Synthetic tumor‐specific breakpoint peptide vaccine in patients with chronic myeloid leukemia and minimal residual disease, Cancer, 115 (2009) 3924-3934. [DOI:10.1002/cncr.24468]

27. [27] K. Cathcart, J. Pinilla-Ibarz, T. Korontsvit, J. Schwartz, V. Zakhaleva, E.B. Papadopoulos, D.A. Scheinberg, A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia, Blood, 103 (2004) 1037-1042. [DOI:10.1182/blood-2003-03-0954]

28. [28] P.S. Kim, P.P. Lee, D. Levy, Dynamics and potential impact of the immune response to chronic myelogenous leukemia, PLoS computational biology, 4 (2008) e1000095. [DOI:10.1371/journal.pcbi.1000095]

29. [29] J. Pinilla-Ibarz, K. Cathcart, T. Korontsvit, S. Soignet, M. Bocchia, J. Caggiano, L. Lai, J. Jimenez, J. Kolitz, D. Scheinberg, Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses, Blood, 95 (2000) 1781-1787. [DOI:10.1182/blood.V95.5.1781.005k46_1781_1787]

30. [30] M. Bocchia, S. Gentili, E. Abruzzese, A. Fanelli, F. Iuliano, A. Tabilio, M. Amabile, F. Forconi, A. Gozzetti, D. Raspadori, Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial, The Lancet, 365 (2005) 657-662. [DOI:10.1016/S0140-6736(05)17945-8]

31. [31] J. Rojas, K. Knight, L. Wang, R. Clark, Clinical evaluation of BCR-ABL peptide immunisation in chronic myeloid leukaemia: results of the EPIC study, Leukemia, 21 (2007) 2287-2295. [DOI:10.1038/sj.leu.2404858]

32. [32] P.G. Maslak, T. Dao, M. Gomez, S. Chanel, J. Packin, T. Korontsvit, V. Zakhaleva, J. Pinilla-Ibarz, E. Berman, D.A. Scheinberg, A pilot vaccination trial of synthetic analog peptides derived from the BCR-ABL breakpoints in CML patients with minimal disease, Leukemia, 22 (2008) 1613-1616. [DOI:10.1038/leu.2008.7]

33. [33] M. Bocchia, M. Defina, L. Aprile, M. Ippoliti, R. Crupi, M. Rondoni, A. Gozzetti, F. Lauria, Complete molecular response in CML after p210 BCR-ABL1-derived peptide vaccination, Nat Rev Clin Oncol, 7 (2010) 600-603. [DOI:10.1038/nrclinonc.2010.141]

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