[논문]Preclinical safety assessment of a therapeutic human papillomavirus DNA vaccine combined with intravaginal interleukin-7 fused with hybrid Fc in female rats

Han, Kang-Hyun; Jang, Min Seong; Han, Hyoung-Yun; Im, Wan-Jung; Jung, Kyung Jin; Park, Ki Seok; Choi, Donghoon; Jeong, Hye Gwang; Kim, Sang Kyum; Moon, Kyoung-Sik

doi:10.1016/j.taap.2021.115406

[해외논문] Preclinical safety assessment of a therapeutic human papillomavirus DNA vaccine combined with intravaginal interleukin-7 fused with hybrid Fc in female rats

Toxicology and applied pharmacology, v.413, 2021년, pp.115406 -

Han, Kang-Hyun (College of Pharmacy, Chungnam National University) , Jang, Min Seong (Department of Advanced Toxicology Research, Korea Institute of Toxicology) , Han, Hyoung-Yun (Department of Predictive Toxicology, Korea Institute of Toxicology) , Im, Wan-Jung (Department of Advanced Toxicology Research, Korea Institute of Toxicology) , Jung, Kyung Jin (Department of Advanced Toxicology Research, Korea Institute of Toxicology) , Park, Ki Seok (Research Institute) , Choi, Donghoon (Research Institute) , Jeong, Hye Gwang (College of Pharmacy, Chungnam National University) , Kim, Sang Kyum (College of Pharmacy, Chungnam National University) , Moon, Kyoung-Sik (Department of Advanced Toxicology Research, Korea Institute of Toxicology)

Abstract ▼ AI-Helper

Abstract This study was conducted to establish the toxicological profile of combination treatment with therapeutic HPV DNA vaccines (GX-188E) and the long-acting form of recombinant human interleukin-7 fused with hybrid Fc (IL-7hyFc). GX-188E was administered intramuscularly by electroporation with or without IL-7hyFc intravaginally once per 2 weeks for 8 weeks (five times) in female Sprague-Dawley rats. Because up-regulation of immune responses and migration of antigen-specific T cells in cervicoviginal tissue were predicted as therapeutic effects, we distinguished adverse effects from therapeutic effects based on the severity of the systemic immune response, reversibility of lymphoid tissue changes, target tissue damage, and off-target immune responses. We observed that the number of neutrophils was increased, and the number of lymphocytes was decreased in the blood. Further, myofiber degeneration, necrosis, fibroplasia, and cell infiltration were observed at the GX-188E administration site. These changes were fully or partially recovered over a 4-week period. Analysis of lymphocytes in spleen revealed that CD4+ T cells and total T cells decreased in rats treated with GX-188E in combination with a high dose of IL-7hyFc (1.25 mg/animal). However, these changes were not considered adverse because they were transient and may have been related to electroporation-mediated DNA delivery or the local migration of lymphocytes induced by IL-7. Therefore, the potential toxicity of the combination of GX-188E and IL-7hyFc treatment was comparable to that of GX-188E treatment alone, and the no observed adverse effect level for GX-188E with IL-7hyFc was considered as 320 μg/animal for GX-188E and 1.25 mg/animal for IL-7hyFc. Highlights Preclinical safety of therapeutic HPV DNA vaccine (GX-188E) and local IL-7hyFc combination treatment. Potential adverse effects of this combination were comparable to HPV DNA vaccine alone. The NOAEL for this combination is 320 μg/animal for GX-188E and 1.25 mg/animal for IL-7hyFc. Graphical abstract [DISPLAY OMISSION]

Keyword

참고문헌 (33)

J. Immunol. Abraham 149 3719 1992 10.4049/jimmunol.149.11.3719 Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-specific pulmonary secretory antibody response

상세보기
J. Biotechnol. Babiuk 110 1 2004 10.1016/j.jbiotec.2004.01.015 Increased gene expression and inflammatory cell infiltration caused by electroporation are both important for improving the efficacy of DNA vaccines

상세보기
Int. J. Oncol. Boda 52 637 2018 Human papilloma virus: apprehending the link with carcinogenesis and unveiling new research avenues (review)

상세보기
Medicine (Baltimore) Chen 97 2018 The risk factors of residual lesions and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive-margin after conization
Expert. Opin. Biol. Ther. Chiarella 8 1645 2008 10.1517/14712598.8.11.1645 Electroporation of skeletal muscle induces danger signal release and antigen-presenting cell recruitment independently of DNA vaccine administration

상세보기
Clin. Cancer Res. Choi 22 5898 2016 10.1158/1078-0432.CCR-16-0423 Intravaginal administration of Fc-fused IL7 suppresses the cervicovaginal tumor by recruiting HPV DNA vaccine-induced CD8 T cells

상세보기
Blood. Colombetti 113 6629 2009 10.1182/blood-2008-05-155309 IL-7 adjuvant treatment enhances long-term tumor-antigen-specific CD8+ T-cell responses after immunization with recombinant lentivector

상세보기
Bull. World Health Organ. Cutts 85 719 2007 10.2471/BLT.06.038414 Human papillomavirus and HPV vaccines: a review

상세보기
Mucosal Immunol. Domingos-Pereira 6 393 2013 10.1038/mi.2012.83 Intravaginal TLR agonists increase local vaccine-specific CD8 T cells and human papillomavirus-associated genital-tumor regression in mice

상세보기
Rev. Med. Virol. Doorbar 25 Suppl. 1 2 2015 10.1002/rmv.1822 Human papillomavirus molecular biology and disease association

상세보기
Lab. Anim. Festing 52 341 2018 10.1177/0023677217738268 On determining sample size in experiments involving laboratory animals

상세보기
JCI Insight Francois 3 2018 10.1172/jci.insight.98960 Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial

상세보기
J. Natl. Cancer Inst. Holowaty 91 252 1999 10.1093/jnci/91.3.252 Natural history of dysplasia of the uterine cervix

상세보기
N. Engl. J. Med. Kenter 361 1838 2009 10.1056/NEJMoa0810097 Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia

상세보기
Nat. Commun. Kim 5 5317 2014 10.1038/ncomms6317 Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients

상세보기
Lancet Oncol. Kocken 12 441 2011 10.1016/S1470-2045(11)70078-X Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study

상세보기
Lancet Kyrgiou 367 489 2006 10.1016/S0140-6736(06)68181-6 Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis

상세보기
Expert Opin. Drug Deliv. Lambricht 13 295 2016 10.1517/17425247.2016.1121990 Clinical potential of electroporation for gene therapy and DNA vaccine delivery

상세보기
Expert. Opin. Biol. Ther. Luxembourg 7 1647 2007 10.1517/14712598.7.11.1647 Electroporation-based DNA immunisation: translation to the clinic

상세보기
Nat. Rev. Immunol. Mackall 11 330 2011 10.1038/nri2970 Harnessing the biology of IL-7 for therapeutic application

상세보기
Sci. Transl. Med. Maldonado 6 221ra13 2014 10.1126/scitranslmed.3007323 Intramuscular therapeutic vaccination targeting HPV16 induces T cell responses that localize in mucosal lesions

상세보기
Nat. Med. Pellegrini 15 528 2009 10.1038/nm.1953 Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies

상세보기
Sci. Transl. Med. Sandoval 5 2013 10.1126/scitranslmed.3004888 Mucosal imprinting of vaccine-induced CD8(+) T cells is crucial to inhibit the growth of mucosal tumors

상세보기
Hum. Vaccine Schalk 2 45 2006 10.4161/hv.2.2.2620 Preclinical and clinical safety studies on DNA vaccines
Vaccine. Schiller 26 Suppl. 10 K53 2008 10.1016/j.vaccine.2008.06.002 An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results

상세보기
Nature Shin 491 463 2012 10.1038/nature11522 A vaccine strategy that protects against genital herpes by establishing local memory T cells

상세보기
Clin. Cancer Res. Soong 20 5456 2014 10.1158/1078-0432.CCR-14-0344 Toll-like receptor agonist imiquimod facilitates antigen-specific CD8+ T-cell accumulation in the genital tract leading to tumor control through IFNgamma

상세보기
Clin. Cancer Res. Sportès 16 727 2010 10.1158/1078-0432.CCR-09-1303 Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy

상세보기
Sci. Rep. Todorova 7 4122 2017 10.1038/s41598-017-04547-2 Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques

상세보기
J. Leukoc. Biol. Toka 78 178 2005 10.1189/jlb.1004621 Mucosal application of plasmid-encoded IL-15 sustains a highly protective anti-herpes simplex virus immunity

상세보기
J. Immunol. Trimble 185 7107 2010 10.4049/jimmunol.1002756 Human papillomavirus 16-associated cervical intraepithelial neoplasia in humans excludes CD8 T cells from dysplastic epithelium

상세보기
N. Engl. J. Med. van Seters 358 1465 2008 10.1056/NEJMoa072685 Treatment of vulvar intraepithelial neoplasia with topical imiquimod

상세보기
Proc. Natl. Acad. Sci. U. S. A. Welters 107 11895 2010 10.1073/pnas.1006500107 Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses

상세보기

LOADING...

활용도 분석정보

상세보기

다운로드

내보내기

활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
더보기 버튼을 클릭하시면 더 많은 관련자료를 살펴볼 수 있습니다.

원문 URL 링크

DOI : 10.1016/j.taap.2021.115406
Elsevier : 저널 > 논문

*원문 PDF 파일 및 링크정보가 존재하지 않을 경우 KISTI DDS 시스템에서 제공하는 원문복사서비스를 사용할 수 있습니다.

저작권 관리 안내

내보내기 메뉴

내보내기 구분

파일저장
인쇄
메일전송

구성항목

기본정보
상세정보

관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관

저장형식

Text(ASCII format)
Excel format
RefWorks Direct Export
RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley

메일정보

받는사람 (필수): @
보내는사람 (선택): @
제목
내용: KISTI 검색결과 이메일 서비스

안내

총 건의 자료가 검색되었습니다.

다운받으실 자료의 인덱스를 입력하세요. (1-10,000)

검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다.

데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요)

다운로드 파일은 UTF-8 형태로 저장됩니다.
파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오.

Text(ASCII format)
Excel format

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

AI-Helper ※ AI-Helper는 을 사용합니다.

AI-Helper

안녕하세요, AI-Helper입니다. 좌측 "선택된 텍스트"에서 텍스트를 선택하여 요약, 번역, 용어설명을 실행하세요.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.

연합인증