PURPOSE: Metastatic cervical cancer is a prototypical chemotherapy-refractory epithelial malignancy for which better treatments are needed. Adoptive T-cell therapy (ACT) is emerging as a promising cancer treatment, but its study in epithelial malignancies has been limited. This study was conducted to determine if ACT could mediate regression of metastatic cervical cancer. PATIENTS AND METHODS: Patients enrolled onto this protocol were diagnosed with metastatic cervical cancer and had previously received platinum-based chemotherapy or chemoradiotherapy. Patients were treated with a single infusion of tumor-infiltrating T cells selected when possible for human papillomavirus (HPV) E6 and E7 reactivity (HPV-TILs). Cell infusion was preceded by lymphocyte-depleting chemotherapy and was followed by administration of aldesleukin. RESULTS: Three of nine patients experienced objective tumor responses (two complete responses and one partial response). The two complete responses were ongoing 22 and 15 months after treatment, respectively. One partial response was 3 months in duration. The HPV reactivity of T cells in the infusion product (as measured by interferon gamma production, enzyme-linked immunospot, and CD137 upregulation assays) correlated positively with clinical response (P = .0238 for all three assays). In addition, the frequency of HPV-reactive T cells in peripheral blood 1 month after treatment was positively associated with clinical response (P = .0238). CONCLUSION: Durable, complete regression of metastatic cervical cancer can occur after a single infusion of HPV-TILs. Exploratory studies suggest a correlation between HPV reactivity of the infusion product and clinical response. Continued investigation of this therapy is warranted. Published by the American Society of Clinical Oncology.
PURPOSE:Metastatic cervical cancer is a prototypical chemotherapy-refractory epithelial malignancy for which better treatments are needed. Adoptive T-cell therapy (ACT) is emerging as a promising cancer treatment, but its study in epithelial malignancies has been limited. This study was conducted to determine if ACT could mediate regression of metastatic cervical cancer. PATIENTS AND METHODS: Patients enrolled onto this protocol were diagnosed with metastatic cervical cancer and had previously received platinum-based chemotherapy or chemoradiotherapy. Patients were treated with a single infusion of tumor-infiltrating T cells selected when possible for human papillomavirus (HPV) E6 and E7 reactivity (HPV-TILs). Cell infusion was preceded by lymphocyte-depleting chemotherapy and was followed by administration of aldesleukin. RESULTS: Three of nine patients experienced objective tumor responses (two complete responses and one partial response). The two complete responses were ongoing 22 and 15 months after treatment, respectively. One partial response was 3 months in duration. The HPV reactivity of T cells in the infusion product (as measured by interferon gamma production, enzyme-linked immunospot, and CD137 upregulation assays) correlated positively with clinical response (P = .0238 for all three assays). In addition, the frequency of HPV-reactive T cells in peripheral blood 1 month after treatment was positively associated with clinical response (P = .0238). CONCLUSION: Durable, complete regression of metastatic cervical cancer can occur after a single infusion of HPV-TILs. Exploratory studies suggest a correlation between HPV reactivity of the infusion product and clinical response. Continued investigation of this therapy is warranted. Published by the American Society of Clinical Oncology.
Authors: Paul F Robbins; Richard A Morgan; Steven A Feldman; James C Yang; Richard M Sherry; Mark E Dudley; John R Wunderlich; Azam V Nahvi; Lee J Helman; Crystal L Mackall; Udai S Kammula; Marybeth S Hughes; Nicholas P Restifo; Mark Raffeld; Chyi-Chia Richard Lee; Catherine L Levy; Yong F Li; Mona El-Gamil; Susan L Schwarz; Carolyn Laurencot; Steven A Rosenberg Journal: J Clin Oncol Date: 2011-01-31 Impact factor: 44.544
Authors: Steven A Rosenberg; James C Yang; Richard M Sherry; Udai S Kammula; Marybeth S Hughes; Giao Q Phan; Deborah E Citrin; Nicholas P Restifo; Paul F Robbins; John R Wunderlich; Kathleen E Morton; Carolyn M Laurencot; Seth M Steinberg; Donald E White; Mark E Dudley Journal: Clin Cancer Res Date: 2011-04-15 Impact factor: 12.531
Authors: Maarten L Zandvliet; Ellis van Liempt; Inge Jedema; Simone Kruithof; Michel G D Kester; Henk-Jan Guchelaar; J H Frederik Falkenburg; Pauline Meij Journal: J Immunother Date: 2011-04 Impact factor: 4.456
Authors: Bradley J Monk; Luis Mas Lopez; Juan J Zarba; Ana Oaknin; Carole Tarpin; Wichai Termrungruanglert; Jacquelyn A Alber; Jie Ding; Melissa W Stutts; Lini N Pandite Journal: J Clin Oncol Date: 2010-07-06 Impact factor: 44.544
Authors: James N Kochenderfer; Wyndham H Wilson; John E Janik; Mark E Dudley; Maryalice Stetler-Stevenson; Steven A Feldman; Irina Maric; Mark Raffeld; Debbie-Ann N Nathan; Brock J Lanier; Richard A Morgan; Steven A Rosenberg Journal: Blood Date: 2010-07-28 Impact factor: 22.113
Authors: Mojgan Ahmadzadeh; Aloisio Felipe-Silva; Bianca Heemskerk; Daniel J Powell; John R Wunderlich; Maria J Merino; Steven A Rosenberg Journal: Blood Date: 2008-09-26 Impact factor: 22.113
Authors: Helen E Heslop; Karen S Slobod; Martin A Pule; Gregory A Hale; Alexandra Rousseau; Colton A Smith; Catherine M Bollard; Hao Liu; Meng-Fen Wu; Richard J Rochester; Persis J Amrolia; Julia L Hurwitz; Malcolm K Brenner; Cliona M Rooney Journal: Blood Date: 2009-10-30 Impact factor: 22.113
Authors: Helen J Mackay; Anna Tinker; Eric Winquist; Gillian Thomas; Kenneth Swenerton; Amit Oza; Joana Sederias; Percy Ivy; Elizabeth A Eisenhauer Journal: Gynecol Oncol Date: 2009-09-08 Impact factor: 5.482
Authors: Sanja Stevanović; Sarah R Helman; John R Wunderlich; Michelle M Langhan; Stacey L Doran; Mei Li M Kwong; Robert P T Somerville; Christopher A Klebanoff; Udai S Kammula; Richard M Sherry; James C Yang; Steven A Rosenberg; Christian S Hinrichs Journal: Clin Cancer Res Date: 2018-12-05 Impact factor: 12.531
Authors: Amir Jazaeri; Robert L Coleman; Anil K Sood; Michael M Frumovitz; Pamela T Soliman; Aaron Shafer; Jeffry J Cutrera; Marlana Klinger; Sara E Sharafi; Cynae A L Johnson; Valerie F Villanueva; Emily M Hinchcliff; Andrea Dickens; Katherine E Cain; Jaime E Anderson; Karen H Lu; Shannon N Westin Journal: Gynecol Oncol Date: 2018-09-10 Impact factor: 5.482
Authors: René J Tavera; Marie-Andrée Forget; Young Uk Kim; Donastas Sakellariou-Thompson; Caitlin A Creasy; Ankit Bhatta; Orenthial J Fulbright; Renjith Ramachandran; Shawne T Thorsen; Esteban Flores; Arely Wahl; Audrey M Gonzalez; Christopher Toth; Seth Wardell; Rahmatu Mansaray; Laszlo G Radvanyi; Dan S Gombos; Sapna P Patel; Patrick Hwu; Rodabe N Amaria; Chantale Bernatchez; Cara Haymaker Journal: J Immunother Date: 2018 Nov/Dec Impact factor: 4.456
Authors: Aaron M Miller; Milad Bahmanof; Dietmar Zehn; Ezra E W Cohen; Stephen P Schoenberger Journal: Cancer Immunol Res Date: 2018-11-27 Impact factor: 11.151