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New Development Models in Immunotherapy

Year 2017, Volume: 9 Issue: 2, 171 - 177, 15.03.2017

Abstract

Abstract

In the treatment of allergic diseases, allergen specific immunotherapy (SIT) is theonly specific treatment method that provide cure and long term protective effect. Although SIT have been used over the past one hundred years, there are still some problems about side effects and efficacy of immunotherapy. Furthermore taking a longtime of treatment causes loss of labor and time, hence new studies on allergen models and use of administration of SIT  is made. In all of these administrations the standardization of allergen extract which has the most effective immun stimulation  concentration and lowest observed adverse effect level is important. There is a need forresearch about long term efficacy, safety, prevention asthma and new allergen sen-sitization of new developed immunotherapy models and allergen extract. This article reviews new developed immunotherapy materials and administration methods.

References

  • Kaynaklar 1.Noon L. Prophylactic inoculation against hay fever. Lancet1911;1:1572-3. 2.Freeman J. Further observations on the treatment of hay fever byhypodermic inoculations of pollen vaccine. Lancet 1911;2:814- 7 3.Ishizaka K, Ishizaka T, Hornbrook MM. Physicochemical pro-perties of human reaginic antibody. Presence of a uniquc immu-noglobulin as a career of reaginic antibody. J Immunol1966;97:75 4.Rocklin RE. Clinical and immunology aspects of allergen speci-fic immunotherapy in patients with seasonal allergic rhinitis and/ or allergic asthma. J Allergy Clin Immunol 1983;72:323 5.Hochfelder JL, Ponda P. Allergen immunotherapy:routes, safety,efficacy, and mode of action. Immuno Targets and Therapy2013;2:61-71 6.Jutel M, Agache I, Bonini S, Burks AW, Calderon M, CanonicaW et al. International consensus on allergy immunotherapy. J Al-lergy Clin Immunol 2015;136:556-68. 7.Scadding GK, Brostoff J. Low dose sublingual therapy in pati-ents with allergic rhinitis due to dust mite. Clin Allergy1986;16:483- 91. 8.Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I,et al. Allergen immunotherapy: a practice parameter third up-date. J Allergy Clin Immunol 2011;127 (1 Suppl):1-55 9.Allam JP, Niederhagen B, Bucheler M, Appel T, Betten H, Bie-ber T et al. Comparative analysis of nasal and oral mucosa den-dritic cells. Allergy 2006; 61:166-72. 10.Jutel M, Agache I, Bonini S, Burks AW, Calderon M, CanonicaW, et al. International consensus on allergy immunotherapy. JAllergy Clin Immunol 2015;136(3):556-6811.Özdemir C, Bahçeciler N, Barlan I. Sublingual İmmunoterapi.Güncel Pediatri 2006; 3: 137-139. 12.Di Bona D, Plaia A, Leto-Barone MS, La Piana S, Di LorenzoG. Efficacy of subcutaneous and sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a meta-analysis-based comparison. J Allergy Clin Immunol. 2012; 130(5):1097–1107. e1092. 13.Wahn U, Tabar A, Kuna P, Halken S, Montagut A, de BeaumontO, Le Gall M; SLIT Study Group. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhi-noconjunctivitis. J Allergy Clin Immunol. 2009 Jan;123(1):160-166. 14.Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Kli-mek L, et al. Safety and efficacy in children of an SQ-standardi-zed grass allergen tablet for sublingual immunotherapy. J AllergyClin Immunol. 2009 Jan;123(1):167-173.15.de Groot H, Bijl A. Anaphylactic reaction after the first dose ofsublingual immunotherapy with grass pollen tablet. Allergy.2009;64(6): 963–964. 34. 16.Vovolis V, Kalogiros L, Mitsias D, Sifnaios E. Severe repeatedanaphylactic reactions to sublingual immunotherapy. Allergol Im-munopathol (Madr). Epub December 17, 2012. 17.Calderón MA, Simons FE, Malling HJ, Lockey RF, Moingeon P,Demoly P. Sublingual allergen immunotherapy: mode of actionand its relationship with the safety profile. Allergy. 2012Mar;67(3):302-11. 18.Litwin A, Flanagan M, Entis G, Gottschlich G, Esch R, Gartsi-de P, et al. Immunologic effects of encapsulated short ragweedextract: a potent new agent for oral immunotherapy. Ann AllergyAsthma Immunol. 1996;77(2):132–138. 19.Litwin A, Flanagan M, Entis G, Gottschlich G, Esch R, Gartsi-de P, et al. Oral immunotherapy with short ragweed extract ina novel encapsulated preparation: a double-blind study. J AllergyClin Immunol. 1997;100(1):30–38. 20.Oppenheimer J, Areson JG, Nelson HS. Safety and efficacy of oralimmunotherapy with standardized cat extract. J Allergy Clin Im-munol. 1994;93:61–67. 21.Urbanek R, Bürgelin KH, Kahle S, Kuhn W, Wahn U. Oral im-munotherapy with grass pollen in enterosoluble capsules. A pros-pective study of the clinical and immunological response. Eur JPediatr. 1990;149(8):545–550 22.Sánchez Palacios A, Schamann Medina F, Lamas Rua-FigueroaA, Bosch Millares C, Ramos Santos S, García Marrero JA. Com-parative clinical-immunological study of oral and subcutaneo-us immunotherapy in children with extrinsic bronchial asthma.Allergol Immunopathol (Madr). 1989;17(6):323–329. 23.Casale TB, Stokes JR. Immunotherapy: what lies beyond. J Al-lergy Clin Immunol. 2014;133(3):612-9: 24.Johansen P, von Moos S, Mohanan D, Kündig TM, Senti G. Newroutes for allergen immunotherapy. Hum Vaccin Immunother.2012;8(10):1525-33. 25.Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R,McCormack SJ, et al. Intralymphatic allergen administration ren-ders specific immunotherapy faster and safer: a randomized con-trolled trial. Proc Natl Acad Sci U S A. 2008 Nov18;105(46):17908-12. 26.Senti G, Crameri R, Kuster D, Johansen P, Martinez-Gomez JM,Graf N, et al. Intralymphatic immunotherapy for cat allergy in-duces tolerance after only 3 injections. J Allergy Clin Immunol.2012;129(5):1290-6. 27.Witten M, Malling HJ, Blom L, Poulsen BC, Poulsen LK. Is intralymp-hatic immunotherapy ready for clinical use in patients with grasspollen allergy? J Allergy Clin Immunol. 2013;132(5):1248-1252 28.Phillips EW. Relief of hay-fever by intradermal injections of pol-len extract. JAMA 1926; 86:182-4; http://dx.doi.org/10.1001/jama.1926.02670290022008. 29.Senti G, Graf N, Haug S, Rüedi N, von Moos S, Sonderegger T,Johansen P, Kündig TM. Epicutaneous allergen administrationas a novel method of allergen-specific immunotherapy. J AllergyClin Immunol. 2009;124(5):997-1002. 30.Senti G, von Moos S, Tay F, Graf N, Sonderegger T, JohansenP, Kündig TM. Epicutaneous allergen-specific immunotherapyameliorates grass pollen-induced rhinoconjunctivitis: A double-blind, placebo-controlled dose escalation study. J Allergy ClinImmunol. 2012;129(1):128-35. 31.Dupont C, Kalach N, Soulaines P, Legoué-Morillon S, PiloquetH, Benhamou PH. Cow's milk epicutaneous immunotherapy inchildren: a pilot trial of safety, acceptability, and impact on al-lergic reactivity. J Allergy Clin Immunol. 2010;125(5):1165-7. 32.Kussebi F, Karamloo F, Rhyner C, Schmid-Grendelmeier P, Sa-lagianni M, Mannhart C, et al: A major allergen gene-fusion pro-tein for potential usage in allergen-specific immunotherapy. J Al-lergy Clin Immunol 2005, 115:323–329. 33.Karamloo F, Schmid-Grendelmeier P, Kussebi F, Akdis M, Sa-lagianni M, von Beust BR, et al: Prevention of allergy by a re-combinant multi-allergen vaccine with reduced IgE binding andpreserved T cell epitopes. Eur J Immunol 2005, 35:3268–3276. 34.Asturias JA, Ibarrola I, Arilla MC, Vidal C, Ferrer A, GamboaPM,et al: Engineering of major house dust mite allergens Der p1 and Der p 2 for allergen-specific immunotherapy. Clin Exp Al-lergy 2009, 39:1088–1098. 35.Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Va-lent P, et al: Vaccination with genetically engineered allergensprevents progression of allergic disease. Proc Natl Acad Sci US A 2004, 101(Suppl 2):14677–14682. 36.Worm M, Lee HH, Kleine-Tebbe J, Hafner RP, Laidler P, Hea-ley D, et al: Development and preliminary clinical evaluation ofa peptide immunotherapy vaccine for cat allergy. J Allergy ClinImmunol 2011, 27:89–97. 97 e81-14. 37.van de Veen W, Stanic B, Yaman G, Wawrzyniak M, Sollner S,Akdis DG,et al: IgG4 production is confined to human IL-10-pro-ducing regulatory B cells that suppress antigen-specific immu-ne responses. J Allergy Clin Immunol 2013, 131:1204–1212 38.Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O: Al-lergen-specific immunotherapy with recombinant grass pollen al-lergens. J Allergy Clin Immunol 2005, 116:608–613 39.Cromwell O, Hafner D, Nandy A: Recombinant allergens for spe-cific immunotherapy. J Allergy Clin Immunol 2011, 127:865–872. 40.Wild C, Wallner M, Hufnagl K, Fuchs H, Hoffmann-Sommerg-ruber K, Breiteneder H, et al: A recombinant allergen chimer asnovel mucosal vaccine candidate for prevention of multi-sensi-tivities. Allergy 2007, 62:33–41. 41.Akdiş M. New treatments for allergen immunotherapy. World Al-lergy Organ J. 2014 Sep 24;7(1):23. 42.Kucuksezer UC, Palomares O, Ruckert B, Jartti T, Puhakka T,Nandy A, et al: Triggering of specific Toll-like receptors and pro-inflammatory cytokines breaks allergen-specific T-cell toleran-ce in human tonsils and peripheral blood. J Allergy Clin Immu-nol 2013, 131:875–885. 43.Zhu D, Kepley CL, Zhang M, Zhang K, Saxon A: A novel humanimmunoglobulin Fc gamma Fc epsilon bifunctional fusion pro-tein inhibits Fc epsilon RI-mediated degranulation. Nat Med 2002,8:518–521. 44.Crameri R, Kundig TM, Akdis CA: Modular antigen-transloca-tion as a novel vaccine strategy for allergen-specific immunot-herapy. Curr Opin Allergy Clin Immunol 2009, 9:568–573. 45.Massanari M, Nelson H, Casale T, Busse W, Kianifard F, GebaGP, Zeldin RK: Effect of pretreatment with omalizumab on thetolerability of specific immunotherapy in allergic asthma. J Al-lergy Clin Immunol 2010, 125:383–389.

Yeni Geliştirilen İmmunoterapi Modelleri

Year 2017, Volume: 9 Issue: 2, 171 - 177, 15.03.2017

Abstract

Öz

Alerjen spesifik immünoterapi (SİT), alerjik hastalıkların tedavisinde kür sağlayan ve uzun süre koruyucu etkisi olan tek spesifik tedavi yöntemidir. Yüz yılı aşkınsüredir alerjik hastalıkların tedavisinde kullanılmasına rağmen günümüzde halen immunoterapi etkinliği ve yan etkilerine dair problemler yaşanmaktadır. Aynı zamanda uzun tedavi süresinin işgücü ve zaman kaybına yol açması, SİT için yeni uygulama yolları ve alerjen modelleri üzerinde çalışmalar yapılmasına neden olmaktadır.Tüm bu uygulamaların hepsinde immün sistemi en iyi uyarabilecek en az yan etkiye sahip doz ve konsantrasyonda alerjen ekstresinin standardizasyonu önem taşımaktadır. Yeni geliştirilen immunoterapi modelleri ve alerjen ekstrelerinin uzun dönemetkinlik, güvenilirlik, astım gelişiminin ve yeni alerjik duyarlanmaların önlenmesikonusunda yapılacak çalışmalara ihtiyaç bulunmaktadır. Bu makalede  yeni geliştirilen immünoterapi materyalleri ve yeni uygulama yöntemlerinden sözedilecektir.

References

  • Kaynaklar 1.Noon L. Prophylactic inoculation against hay fever. Lancet1911;1:1572-3. 2.Freeman J. Further observations on the treatment of hay fever byhypodermic inoculations of pollen vaccine. Lancet 1911;2:814- 7 3.Ishizaka K, Ishizaka T, Hornbrook MM. Physicochemical pro-perties of human reaginic antibody. Presence of a uniquc immu-noglobulin as a career of reaginic antibody. J Immunol1966;97:75 4.Rocklin RE. Clinical and immunology aspects of allergen speci-fic immunotherapy in patients with seasonal allergic rhinitis and/ or allergic asthma. J Allergy Clin Immunol 1983;72:323 5.Hochfelder JL, Ponda P. Allergen immunotherapy:routes, safety,efficacy, and mode of action. Immuno Targets and Therapy2013;2:61-71 6.Jutel M, Agache I, Bonini S, Burks AW, Calderon M, CanonicaW et al. International consensus on allergy immunotherapy. J Al-lergy Clin Immunol 2015;136:556-68. 7.Scadding GK, Brostoff J. Low dose sublingual therapy in pati-ents with allergic rhinitis due to dust mite. Clin Allergy1986;16:483- 91. 8.Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I,et al. Allergen immunotherapy: a practice parameter third up-date. J Allergy Clin Immunol 2011;127 (1 Suppl):1-55 9.Allam JP, Niederhagen B, Bucheler M, Appel T, Betten H, Bie-ber T et al. Comparative analysis of nasal and oral mucosa den-dritic cells. Allergy 2006; 61:166-72. 10.Jutel M, Agache I, Bonini S, Burks AW, Calderon M, CanonicaW, et al. International consensus on allergy immunotherapy. JAllergy Clin Immunol 2015;136(3):556-6811.Özdemir C, Bahçeciler N, Barlan I. Sublingual İmmunoterapi.Güncel Pediatri 2006; 3: 137-139. 12.Di Bona D, Plaia A, Leto-Barone MS, La Piana S, Di LorenzoG. Efficacy of subcutaneous and sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a meta-analysis-based comparison. J Allergy Clin Immunol. 2012; 130(5):1097–1107. e1092. 13.Wahn U, Tabar A, Kuna P, Halken S, Montagut A, de BeaumontO, Le Gall M; SLIT Study Group. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhi-noconjunctivitis. J Allergy Clin Immunol. 2009 Jan;123(1):160-166. 14.Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Kli-mek L, et al. Safety and efficacy in children of an SQ-standardi-zed grass allergen tablet for sublingual immunotherapy. J AllergyClin Immunol. 2009 Jan;123(1):167-173.15.de Groot H, Bijl A. Anaphylactic reaction after the first dose ofsublingual immunotherapy with grass pollen tablet. Allergy.2009;64(6): 963–964. 34. 16.Vovolis V, Kalogiros L, Mitsias D, Sifnaios E. Severe repeatedanaphylactic reactions to sublingual immunotherapy. Allergol Im-munopathol (Madr). Epub December 17, 2012. 17.Calderón MA, Simons FE, Malling HJ, Lockey RF, Moingeon P,Demoly P. Sublingual allergen immunotherapy: mode of actionand its relationship with the safety profile. Allergy. 2012Mar;67(3):302-11. 18.Litwin A, Flanagan M, Entis G, Gottschlich G, Esch R, Gartsi-de P, et al. Immunologic effects of encapsulated short ragweedextract: a potent new agent for oral immunotherapy. Ann AllergyAsthma Immunol. 1996;77(2):132–138. 19.Litwin A, Flanagan M, Entis G, Gottschlich G, Esch R, Gartsi-de P, et al. Oral immunotherapy with short ragweed extract ina novel encapsulated preparation: a double-blind study. J AllergyClin Immunol. 1997;100(1):30–38. 20.Oppenheimer J, Areson JG, Nelson HS. Safety and efficacy of oralimmunotherapy with standardized cat extract. J Allergy Clin Im-munol. 1994;93:61–67. 21.Urbanek R, Bürgelin KH, Kahle S, Kuhn W, Wahn U. Oral im-munotherapy with grass pollen in enterosoluble capsules. A pros-pective study of the clinical and immunological response. Eur JPediatr. 1990;149(8):545–550 22.Sánchez Palacios A, Schamann Medina F, Lamas Rua-FigueroaA, Bosch Millares C, Ramos Santos S, García Marrero JA. Com-parative clinical-immunological study of oral and subcutaneo-us immunotherapy in children with extrinsic bronchial asthma.Allergol Immunopathol (Madr). 1989;17(6):323–329. 23.Casale TB, Stokes JR. Immunotherapy: what lies beyond. J Al-lergy Clin Immunol. 2014;133(3):612-9: 24.Johansen P, von Moos S, Mohanan D, Kündig TM, Senti G. Newroutes for allergen immunotherapy. Hum Vaccin Immunother.2012;8(10):1525-33. 25.Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R,McCormack SJ, et al. Intralymphatic allergen administration ren-ders specific immunotherapy faster and safer: a randomized con-trolled trial. Proc Natl Acad Sci U S A. 2008 Nov18;105(46):17908-12. 26.Senti G, Crameri R, Kuster D, Johansen P, Martinez-Gomez JM,Graf N, et al. Intralymphatic immunotherapy for cat allergy in-duces tolerance after only 3 injections. J Allergy Clin Immunol.2012;129(5):1290-6. 27.Witten M, Malling HJ, Blom L, Poulsen BC, Poulsen LK. Is intralymp-hatic immunotherapy ready for clinical use in patients with grasspollen allergy? J Allergy Clin Immunol. 2013;132(5):1248-1252 28.Phillips EW. Relief of hay-fever by intradermal injections of pol-len extract. JAMA 1926; 86:182-4; http://dx.doi.org/10.1001/jama.1926.02670290022008. 29.Senti G, Graf N, Haug S, Rüedi N, von Moos S, Sonderegger T,Johansen P, Kündig TM. Epicutaneous allergen administrationas a novel method of allergen-specific immunotherapy. J AllergyClin Immunol. 2009;124(5):997-1002. 30.Senti G, von Moos S, Tay F, Graf N, Sonderegger T, JohansenP, Kündig TM. Epicutaneous allergen-specific immunotherapyameliorates grass pollen-induced rhinoconjunctivitis: A double-blind, placebo-controlled dose escalation study. J Allergy ClinImmunol. 2012;129(1):128-35. 31.Dupont C, Kalach N, Soulaines P, Legoué-Morillon S, PiloquetH, Benhamou PH. Cow's milk epicutaneous immunotherapy inchildren: a pilot trial of safety, acceptability, and impact on al-lergic reactivity. J Allergy Clin Immunol. 2010;125(5):1165-7. 32.Kussebi F, Karamloo F, Rhyner C, Schmid-Grendelmeier P, Sa-lagianni M, Mannhart C, et al: A major allergen gene-fusion pro-tein for potential usage in allergen-specific immunotherapy. J Al-lergy Clin Immunol 2005, 115:323–329. 33.Karamloo F, Schmid-Grendelmeier P, Kussebi F, Akdis M, Sa-lagianni M, von Beust BR, et al: Prevention of allergy by a re-combinant multi-allergen vaccine with reduced IgE binding andpreserved T cell epitopes. Eur J Immunol 2005, 35:3268–3276. 34.Asturias JA, Ibarrola I, Arilla MC, Vidal C, Ferrer A, GamboaPM,et al: Engineering of major house dust mite allergens Der p1 and Der p 2 for allergen-specific immunotherapy. Clin Exp Al-lergy 2009, 39:1088–1098. 35.Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Va-lent P, et al: Vaccination with genetically engineered allergensprevents progression of allergic disease. Proc Natl Acad Sci US A 2004, 101(Suppl 2):14677–14682. 36.Worm M, Lee HH, Kleine-Tebbe J, Hafner RP, Laidler P, Hea-ley D, et al: Development and preliminary clinical evaluation ofa peptide immunotherapy vaccine for cat allergy. J Allergy ClinImmunol 2011, 27:89–97. 97 e81-14. 37.van de Veen W, Stanic B, Yaman G, Wawrzyniak M, Sollner S,Akdis DG,et al: IgG4 production is confined to human IL-10-pro-ducing regulatory B cells that suppress antigen-specific immu-ne responses. J Allergy Clin Immunol 2013, 131:1204–1212 38.Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O: Al-lergen-specific immunotherapy with recombinant grass pollen al-lergens. J Allergy Clin Immunol 2005, 116:608–613 39.Cromwell O, Hafner D, Nandy A: Recombinant allergens for spe-cific immunotherapy. J Allergy Clin Immunol 2011, 127:865–872. 40.Wild C, Wallner M, Hufnagl K, Fuchs H, Hoffmann-Sommerg-ruber K, Breiteneder H, et al: A recombinant allergen chimer asnovel mucosal vaccine candidate for prevention of multi-sensi-tivities. Allergy 2007, 62:33–41. 41.Akdiş M. New treatments for allergen immunotherapy. World Al-lergy Organ J. 2014 Sep 24;7(1):23. 42.Kucuksezer UC, Palomares O, Ruckert B, Jartti T, Puhakka T,Nandy A, et al: Triggering of specific Toll-like receptors and pro-inflammatory cytokines breaks allergen-specific T-cell toleran-ce in human tonsils and peripheral blood. J Allergy Clin Immu-nol 2013, 131:875–885. 43.Zhu D, Kepley CL, Zhang M, Zhang K, Saxon A: A novel humanimmunoglobulin Fc gamma Fc epsilon bifunctional fusion pro-tein inhibits Fc epsilon RI-mediated degranulation. Nat Med 2002,8:518–521. 44.Crameri R, Kundig TM, Akdis CA: Modular antigen-transloca-tion as a novel vaccine strategy for allergen-specific immunot-herapy. Curr Opin Allergy Clin Immunol 2009, 9:568–573. 45.Massanari M, Nelson H, Casale T, Busse W, Kianifard F, GebaGP, Zeldin RK: Effect of pretreatment with omalizumab on thetolerability of specific immunotherapy in allergic asthma. J Al-lergy Clin Immunol 2010, 125:383–389.
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Details

Primary Language Turkish
Journal Section makale
Authors

Dr. Derya Ufuk Altıntaş

Publication Date March 15, 2017
Published in Issue Year 2017 Volume: 9 Issue: 2

Cite

APA Altıntaş, D. D. U. (2017). Yeni Geliştirilen İmmunoterapi Modelleri. Klinik Tıp Pediatri Dergisi, 9(2), 171-177.
AMA Altıntaş DDU. Yeni Geliştirilen İmmunoterapi Modelleri. Pediatri. March 2017;9(2):171-177.
Chicago Altıntaş, Dr. Derya Ufuk. “Yeni Geliştirilen İmmunoterapi Modelleri”. Klinik Tıp Pediatri Dergisi 9, no. 2 (March 2017): 171-77.
EndNote Altıntaş DDU (March 1, 2017) Yeni Geliştirilen İmmunoterapi Modelleri. Klinik Tıp Pediatri Dergisi 9 2 171–177.
IEEE D. D. U. Altıntaş, “Yeni Geliştirilen İmmunoterapi Modelleri”, Pediatri, vol. 9, no. 2, pp. 171–177, 2017.
ISNAD Altıntaş, Dr. Derya Ufuk. “Yeni Geliştirilen İmmunoterapi Modelleri”. Klinik Tıp Pediatri Dergisi 9/2 (March 2017), 171-177.
JAMA Altıntaş DDU. Yeni Geliştirilen İmmunoterapi Modelleri. Pediatri. 2017;9:171–177.
MLA Altıntaş, Dr. Derya Ufuk. “Yeni Geliştirilen İmmunoterapi Modelleri”. Klinik Tıp Pediatri Dergisi, vol. 9, no. 2, 2017, pp. 171-7.
Vancouver Altıntaş DDU. Yeni Geliştirilen İmmunoterapi Modelleri. Pediatri. 2017;9(2):171-7.