Clinics in Oncology Editorial · 7. 7. Grohmann U, Puccetti P, Belladonna ML, Fallarino F, Bianchi...
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Remedy Publications LLC., | http://clinicsinoncology.com/ Clinics in Oncology 2018 | Volume 3 | Article 1411 1 Drug-Induced Neoantigens: A New Horizon in Cancer Immunotherapy? OPEN ACCESS *Correspondence: Enzo Bonmassar, Department of Systems Medicine, National Council of Research, Rome, Italy, E-mail: [email protected] Received Date: 03 Jan 2018 Accepted Date: 12 Feb 2018 Published Date: 18 Feb 2018 Citation: Franzese O, Aquino A, Fuggetta MP, Roselli M, Bonmassar E, De Vecchis L, et al. Drug-Induced Neoantigens: A New Horizon in Cancer Immunotherapy?. Clin Oncol. 2018; 3: 1411. Copyright © 2018 Bonmassar E. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Published: 18 Feb, 2018 Franzese O 1 , Aquino A 1 , Fuggetta MP 2 , Roselli M 3 , Bonmassar E 1,2 *, De Vecchis L 3 and Torino F 3 1 Department of Systems Medicine, School of Medicine, University of Rome Tor Vergata, Rome, Italy 2 Institute of Translational Pharmacology, National Council of Research, Rome, Italy 3 Department of Systems Medicine, Medical Oncology, University of Rome Tor Vergata, Rome, Italy Editorial Tumor immunology has been neglected for many years. With the recent appearance on the scene of Immune Checkpoint Inhibitors (ICpI, 1) tumor immunology gained a lead role in cancer therapy. In general, classical cytotoxic chemotherapy and targeted therapy has been, at least in part, disappointing due to the almost inevitable onset of resistance in the majority of solid malignancies mostly as a result of mutations affecting target susceptibility to the drug [2]. However, also resistance against ICpI-based immunotherapy in cancer cells of different histological types was soon evident in the clinics, and this is due predominantly to the emergence of scarcely immunogenic neoplastic cell clones [3]. More than 40 years ago, we were the first to demonstrate that in vivo treatment with an antitumor compound of triazene family induces the appearance of strong transplantation antigens in murine leukemia cells [4]. Since then, this phenomenon that we called “chemical xenogenization” and more recently “Drug-induced Xenogenization” (DIX, reviewed in 5) was found to be generated by somatic mutations [6, 7] capable of inducing the synthesis of abnormal proteins. e intracellular processing of these proteins leads to the appearance of non-self peptides that are presented to T cells in the context of MHC [7]. Up-to now, ICpI, that are able to amplify exceedingly T-cell immune reactivity of the host, rely on tumor-associated antigens naturally present in cancer cells, especially in case of cells endowed with high mutation load [8]. We propose now to consider the possibility of a pharmacological control of mutation load. Up-to-date DIX has been found to be generated preferentially by triazenes (e.g. temozolomide). erefore, in the near future a new tactic seems to appear on the skyline of cancer immunotherapy. is consists in the adoption of triazene derivatives or other compounds endowed with potent DIX activity for a successful cancer treatment based on ICpI and Drug- Induced Neoantigens. References 1. Wilson RAM, Evans TRJ, Fraser AR, Nibbs RJB. Immune checkpoint inhibitors: new strategies to checkmate cancer. Clin Exp Immunol. 2017. 2. Mansoori B, Mohammadi A, Davudian S, Shirjang S and Baradaran B. e different mechanisms of cancer drug resistance: A brief review. Adv Pharm Bull. 2017;7(3): 339-348. 3. Syn NL, Teng MWL, Mok TSK, Soo RA. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017;18(12):e731-e741. 4. Bonmassar E, Bonmassar A, Vadlamudi S, Goldin A. Immunological alteration of leukemic cells in vivo aſter treatment with an antitumor drug. Proc Natl Acad Sci U S A. 1970;66(4):1089-95. 5. Franzese O, Torino F, Fuggetta MP, Aquino A, Roselli M, Bonmassar E, et al. Tumor immunotherapy: drug- induced neoantigens (xenogenization) and immune checkpoint inhibitors. Oncotarget. 2017;8(25) :41641- 41669. 6. Giampietri A, Fioretti MC, Goldin A, Bonmassar E. Drug-mediated antigenic changes in murine leukemia cells: antagonistic effects of quinacrine, an antimutagenic compound. J Natl Cancer Inst. 1980;64(2):297-301. 7. 7. Grohmann U, Puccetti P, Belladonna ML, Fallarino F, Bianchi R, Binaglia L, Sagakuchi K, Mage MG, Appella E, Fioretti MC. Multiple point mutations in an endogenous retroviral gene confer high immunogenicity on a drug-treated murine tumor. J Immunol. 1995,154:4630-41 8. Capietto AH, Jhunjhunwala S, Delamarre L. Characterizing neoantigens for personalized cancer immunotherapy. Curr Opin Immunol. 2017,46:58-65.
Transcript of Clinics in Oncology Editorial · 7. 7. Grohmann U, Puccetti P, Belladonna ML, Fallarino F, Bianchi...
Remedy Publications LLC., | http://clinicsinoncology.com/
Clinics in Oncology
2018 | Volume 3 | Article 14111
Drug-Induced Neoantigens: A New Horizon in Cancer Immunotherapy?
OPEN ACCESS
*Correspondence:Enzo Bonmassar, Department of
Systems Medicine, National Council of Research, Rome, Italy,
E-mail: [email protected] Date: 03 Jan 2018Accepted Date: 12 Feb 2018Published Date: 18 Feb 2018
Citation: Franzese O, Aquino A, Fuggetta MP, Roselli M, Bonmassar E, De
Vecchis L, et al. Drug-Induced Neoantigens: A New Horizon in Cancer Immunotherapy?. Clin Oncol. 2018; 3:
1411.
Copyright © 2018 Bonmassar E. This is an open access article distributed
under the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work
is properly cited.
EditorialPublished: 18 Feb, 2018
Franzese O1, Aquino A1, Fuggetta MP2, Roselli M3, Bonmassar E1,2*, De Vecchis L3 and Torino F3
1Department of Systems Medicine, School of Medicine, University of Rome Tor Vergata, Rome, Italy
2Institute of Translational Pharmacology, National Council of Research, Rome, Italy
3Department of Systems Medicine, Medical Oncology, University of Rome Tor Vergata, Rome, Italy
EditorialTumor immunology has been neglected for many years. With the recent appearance on the
scene of Immune Checkpoint Inhibitors (ICpI, 1) tumor immunology gained a lead role in cancer therapy. In general, classical cytotoxic chemotherapy and targeted therapy has been, at least in part, disappointing due to the almost inevitable onset of resistance in the majority of solid malignancies mostly as a result of mutations affecting target susceptibility to the drug [2]. However, also resistance against ICpI-based immunotherapy in cancer cells of different histological types was soon evident in the clinics, and this is due predominantly to the emergence of scarcely immunogenic neoplastic cell clones [3].
More than 40 years ago, we were the first to demonstrate that in vivo treatment with an antitumor compound of triazene family induces the appearance of strong transplantation antigens in murine leukemia cells [4]. Since then, this phenomenon that we called “chemical xenogenization” and more recently “Drug-induced Xenogenization” (DIX, reviewed in 5) was found to be generated by somatic mutations [6, 7] capable of inducing the synthesis of abnormal proteins. The intracellular processing of these proteins leads to the appearance of non-self peptides that are presented to T cells in the context of MHC [7].
Up-to now, ICpI, that are able to amplify exceedingly T-cell immune reactivity of the host, rely on tumor-associated antigens naturally present in cancer cells, especially in case of cells endowed with high mutation load [8]. We propose now to consider the possibility of a pharmacological control of mutation load. Up-to-date DIX has been found to be generated preferentially by triazenes (e.g. temozolomide). Therefore, in the near future a new tactic seems to appear on the skyline of cancer immunotherapy. This consists in the adoption of triazene derivatives or other compounds endowed with potent DIX activity for a successful cancer treatment based on ICpI and Drug-Induced Neoantigens.
References1. Wilson RAM, Evans TRJ, Fraser AR, Nibbs RJB. Immune checkpoint inhibitors: new strategies to checkmate
cancer. Clin Exp Immunol. 2017.
2. Mansoori B, Mohammadi A, Davudian S, Shirjang S and Baradaran B. The different mechanisms of cancer drug resistance: A brief review. Adv Pharm Bull. 2017;7(3): 339-348.
3. Syn NL, Teng MWL, Mok TSK, Soo RA. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017;18(12):e731-e741.
4. Bonmassar E, Bonmassar A, Vadlamudi S, Goldin A. Immunological alteration of leukemic cells in vivo after treatment with an antitumor drug. Proc Natl Acad Sci U S A. 1970;66(4):1089-95.
5. Franzese O, Torino F, Fuggetta MP, Aquino A, Roselli M, Bonmassar E, et al. Tumor immunotherapy: drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors. Oncotarget. 2017;8(25) :41641-41669.
6. Giampietri A, Fioretti MC, Goldin A, Bonmassar E. Drug-mediated antigenic changes in murine leukemia cells: antagonistic effects of quinacrine, an antimutagenic compound. J Natl Cancer Inst. 1980;64(2):297-301.
7. 7. Grohmann U, Puccetti P, Belladonna ML, Fallarino F, Bianchi R, Binaglia L, Sagakuchi K, Mage MG, Appella E, Fioretti MC. Multiple point mutations in an endogenous retroviral gene confer high immunogenicity on a drug-treated murine tumor. J Immunol. 1995,154:4630-41
8. Capietto AH, Jhunjhunwala S, Delamarre L. Characterizing neoantigens for personalized cancer immunotherapy. Curr Opin Immunol. 2017,46:58-65.
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