Connie L. Trimble, MD

Primary Academic Title

Professor of Gynecology and Obstetrics

Background

Centers and Institutes

• Cervical Dysplasia Center
• Sidney Kimmel Comprehensive Cancer Center

Clinical Trial Keywords

therapeutic vaccines, HPV, high grade dysplasia, precancerous, alternative HPV treatments, lesion microenvironment

Clinical Trials Summary

J0866 - A Pilot Study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)

J1498 - A Phase I Study of Intravaginally Administered Artesunate In Women with High Grade Cervical Intraepithelial Neoplasia (CIN2/3)

J0656 - A Phase I efficacy and safety study of HPV16-specific therapeutic DNA-Vaccinia vaccination in combination with topical imiquimod, in patients with HPV16 high grade cervical dysplasia (CIN2/3)

Videos

• Innovation, Education, Collaboration

Recent News Articles and Media Coverage

• Creating Vaccines to Kick Cancer's Butt, Tedx Talk (12/2015)
• A Bed Of Mouse Cells Helps Human Cells Thrive In The Lab, NPR (01/2015)

Additional Academic Titles

Professor of Pathology, Professor of Oncology

Research Interests

Cancer Vaccines, Cervical Cancer, HPV, tumor immunology, tumor microenvironment, intraepithelial neoplasia

Lab Website

Cervical Dysplasia Research Lab - Lab Website

• We are interested in how immune responses occur in the cervix. The focus of our translational research is on developing immune therapies for disease caused by human papillomavirus (HPV). HPV infection causes more cancers than any other virus in the world. Cervical cancer is the most common cancer caused by HPV, and although we have known how to screen for it for over half a century, it remains the second most common cause of cancer death in women. Although the preventive vaccines are a public health milestone, they prevent HPV infections, but are not designed to make immune responses to treat HPV. We are testing different strategies to make immune responses that could treat HPV disease. Our dedicated researchers are working to extend the techniques used in HPV vaccine development to the creation of vaccines targeting other cancers with defined tumor antigens.

Selected Publications

• Peng, S.; Tomson, T.T.; Trimble, C.; He, L.; Hung, C.F.; Wu, T.C. A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects. Gene Ther. 2006 Feb;13(3):257-265.

  Peng, S.; Trimble, C.; He, L.; Tsai, Y.C.; Lin, C.T.; Boyd, D.A.; Pardoll, D.; Hung, C.F.; Wu, T.C. Characterization of HLA-A2-restricted HPV-16 E7-specific CD8(+) T-cell immune responses induced by DNA vaccines in HLA-A2 transgenic mice. Gene Ther. 2006 Jan;13(1):67-77.

  Peng, S.; Trimble, C.; Wu, L.; Pardoll, D.; Roden, R.; Hung, C.F.; Wu, T.C. HLA-DQB1*02-restricted HPV-16 E7 peptide-specific CD4+ T-cell immune responses correlate with regression of HPV-16-associated high-grade squamous intraepithelial lesions. Clin Cancer Res. 2007 Apr 15;13(8):2479-2487.

  Partridge, E.E.; Abu-Rustum, N.; Campos, S.; Fahey, P.J.; Greer, B.E.; Lele, S.M.; Lieberman, R.W.; Lipscomb, G.H.; Morgan, M.; Nava, M.E.; Reynolds, R.K.; Singh, D.K.; Smith-McCune, K.; Teng, N.; Trimble, C.L.; Valea, F.; Wilczynski, S.; National Comprehensive Cancer, N. Cervical cancer screening. J Natl Compr Canc Netw. 2008 Jan;6(1):58-82.

  Peng, S.; Trimble, C.; Alvarez, R.D.; Huh, W.K.; Lin, Z.; Monie, A.; Hung, C.F.; Wu, T.C. Cluster intradermal DNA vaccination rapidly induces E7-specific CD8+ T-cell immune responses leading to therapeutic antitumor effects. Gene Ther. 2008 Aug;15(16):1156-1166.

  Trimble, C.L. Human papillomavirus vaccination should be offered to young males: Counterpoint. Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):809.
  Tseng, C.W.; Hung, C.F.; Alvarez, R.D.; Trimble, C.; Huh, W.K.; Kim, D.; Chuang, C.M.; Lin, C.T.; Tsai, Y.C.; He, L.; Monie, A.; Wu, T.C. Pretreatment with cisplatin enhances E7-specific CD8+ T-Cell-mediated antitumor immunity induced by DNA vaccination. Clin Cancer Res. 2008 May 15;14(10):3185-3192.

  Tseng, C.W.; Monie, A.; Trimble, C.; Alvarez, R.D.; Huh, W.K.; Buchsbaum, D.J.; Straughn, J.M., Jr.; Wang, M.C.; Yagita, H.; Hung, C.F.; Wu, T.C. Combination of treatment with death receptor 5-specific antibody with therapeutic HPV DNA vaccination generates enhanced therapeutic anti-tumor effects. Vaccine. 2008 Aug 12;26(34):4314-4319.

  Tseng, C.W.; Trimble, C.; Zeng, Q.; Monie, A.; Alvarez, R.D.; Huh, W.K.; Hoory, T.; Wang, M.C.; Hung, C.F.; Wu, T.C. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts. Cancer Immunol Immunother. 2008 Sep 25.

  Trimble, C.L.; Frazer, I.H. Development of therapeutic HPV vaccines. Lancet Oncol. 2009 Oct;10(10):975-980.

  Trimble, C.L.; Peng, S.; Kos, F.; Gravitt, P.; Viscidi, R.; Sugar, E.; Pardoll, D.; Wu, T.C. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res. 2009 Jan 1;15(1):361-367.

  Trimble, C.L.; Peng, S.; Thoburn, C.; Kos, F.; Wu, T.C. Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3. Cancer Immunol Immunother. 2009 Dec 13.

  Tseng, C.W.; Trimble, C.; Zeng, Q.; Monie, A.; Alvarez, R.D.; Huh, W.K.; Hoory, T.; Wang, M.C.; Hung, C.F.; Wu, T.C. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts. Cancer Immunol Immunother. 2009 May;58(5):737-748.

  Yen, H.R.; Harris, T.J.; Wada, S.; Grosso, J.F.; Getnet, D.; Goldberg, M.V.; Liang, K.L.; Bruno, T.C.; Pyle, K.J.; Chan, S.L.; Anders, R.A.; Trimble, C.L.; Adler, A.J.; Lin, T.Y.; Pardoll, D.M.; Huang, C.T.; Drake, C.G. Tc17 CD8 T cells: functional plasticity and subset diversity. J Immunol. 2009 Dec 1;183(11):7161-7168.

  Trimble, C.L.; Clark, R.A.; Thoburn, C.; Hanson, N.C.; Tassello, J.; Frosina, D.; Kos, F.; Teague, J.; Jiang, Y.; Barat, N.C.; Jungbluth, A.A. Human papillomavirus 16-associated cervical intraepithelial neoplasia in humans excludes CD8 T cells from dysplastic epithelium. J Immunol. 2010 Dec 1;185(11):7107-7114.

  Trimble, C.L.; Peng, S.; Thoburn, C.; Kos, F.; Wu, T.C. Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3. Cancer Immunol Immunother. 2010 May;59(5):799-803

  Zaino RJ, Trimble CL, Silverberg S, Kauderer J, Curtin J.  Reproducibility of the diagnosis of atypical endometrial hyperplasia (AEH): A Gynecologic Oncology Group (GOG) Study. Cancer 2006; 106(4):804-11.

  Trimble CL, Kauderer J, Silverberg S, Curtin J, Lim PC, Burke JJ, Zaino RJ. Concurrent endometrial carcinoma (EC) in women with a biopsy diagnosis of atypical endometrial hyperplasia (AEH): a Gynecologic Oncology Group (GOG) study. Cancer 2006; 106(4):812-9. 

  Trimble CL, Peng S, Kos F, Gravitt P, Viscidi R, Sugar E, Pardoll DM, Wu TC. A phase I trial of human papillomavirus (HPV) DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res 2009; 15(1):361-7.

  Yen HR, Harris TJ, Wata S, Grosso JF, Getnet D, Goldberg MV, Liang KL, Bruno TC, Pyle KJ, Chan SL, Anders RA, Trimble CL, Adler AJ, Lin TY, Pardoll DM, Huang CT, Drake CG. Tc17 CD8 T cells: functional plasticity and subset diversity. J Immunol 2009; 183, 7161-7168.

  Trimble CL, Clark RA, Thoburn C, Hanson NC, Tassello J, Frosina D, Kos F, Teague J, Jiang JE, Barat NC, Jungbluth AA. Human papillomavirus 16-associated cervical intraepithelial neoplasia in humans excludes CD8 T cells from dysplastic epithelium.  J Immunol 2010; 185(11):7107-7114

  Chou B, Krill LS, Horton BB, Barat CE, Trimble, CL. Disparities in human papillomavirus vaccine completion among vaccine initiators.  Obstet Gynecol 2011; 118(1):14-20.

  Levenback CF, Ali S, Coleman RL, Gold MA, Fowler JM, Judson P, Bell MC, De Geest K, Spirtos N, Potkul RK, Leitao MM, Bakkum-Gamez JN, Rossi EC, Lentz SS, Burke II JJ, Van Le L, Trimble CL. Lymphatic Mapping and Sentinel Lymph Node Biopsy in Women with Squamous Carcinoma of the Vulva: A Gynecologic Oncology Group Study. J Clin Oncol 2012; 30(31):3786-91.

  Wallbillich JJ, Rhodes H, Milbourne A, Munsell M, Frumovitz M, Brown J, Trimble CL, Schmeler KM. Vulvar intraepithelial neoplasia (VIN2/3): comparing clinical outcomes and evaluating risk factors for recurrence.  Gynecol Oncol, 2012; 127(2):312-5.

  Coleman RL, Ali S, Levenback CF, Gold MA, Fowler JM, Judson PL, Bell MC, De Geest K, Spirtos NM, Potkul RK, Leitao MM Jr, Bakkum-Gamez JN, Rossi EC, Lentz SS, Burke JJ 2nd, Van Le L, Trimble CL.  Is bilateral lymphadenectomy for midline squamous carcinoma of the vulva always necessary?  An analysis from Gynecologic Oncology Group (GOG) 173.  Gynecol Oncol, 2013; 128:155-159.

  Maldonado L, Teague JE, Morrow MP, Yotova I, Wu TC, Wang C, Desmarais C, Boyer JD, Tycko B, Robins HS, Clark RA, Trimble CL.  Intramuscular therapeutic vaccination targeting HPV16 induces T cell responses that localize in mucosal lesions. Sci Transl Med 2014; 6,(221):221ra13.

  Trimble CL, Method M, Leitao M, Lu K, Ioffee O, Hampton M, Higgins R, Zaino R, Mutter GL.  Management of endometrial precancers. Obstet Gynecol,; 2012 Nov;120(5):1160-1175.

  Stanley M, Pinto LA, Trimble C.  Human papillomavirus vaccines – immune responses. Vaccine 2012 Nov 20; Supple5:F83-7. 

   

  Trimble CL. HPV Infection-Associated Cancers: Next-Generation Technology for Diagnosis and Treatment. Cancer Immunology at the Crossroads series, Cancer Immunol Res, 2014 Oct;2(10):937-942.