Adoptive T-Cell Therapy for Cervical Cancer
Cell-based therapies with lymphocytes and antigen-presenting cells are promising approaches in the context of cancer immunotherapy. Transfusion of T-cells, also called adoptive cell therapy, effectively treats viral infections, and has induced responses in early-stage clinical trials among cancer patients.1
Hinrichs and colleagues presented data regarding use of human papillomavirus (HPV)-targeted tumor-infiltrating lymphocytes for cervical cancer, a virally induced malignancy that expresses HPV E6 and E7 oncoproteins (ASCO 2014; Abstract LBA3008).
Treatment for patients with recurrent cervical cancer that has spread beyond the confines of a radiation or surgical field is not standardized. While cytotoxic chemotherapy, including platinum agents and taxanes are options, as well as bevacizumab, can be effective for selected patients, women with cervical cancer are appropriate candidates for clinical trials testing drug combinations or new anticancer agents.2
This phase 1 clinical trial enrolled patients with metastatic HPV-positive cancers with tumor-infiltrating lymphocytes selected for HPV E6 and E7 reactivity (HPV-TIL), including women with metastatic cervical cancer. In this study, HPV-TIL infusion was preceded by nonmyeloablative conditioning and followed by high-dose aldesleukin.
Nine patients with metastatic cervical cancer were treated, receiving a median of 81 x 109 T-cells (range, 33-159 x 109) as a single infusion. The infused cells possessed reactivity against high-risk HPV E6 and/or E7 in 6 of 8 patients. The 2 patients with no HPV reactivity did not respond to treatment.
Three of the 6 patients with HPV reactivity demonstrated objective tumor responses by RECIST, including 2 complete responses and 1 partial response. A fourth patient had best response of 39% reduction in tumor size.
Both of the patients with complete responses to HPV-TIL infusion had widespread metastases and both continue to respond 11 and 18 months posttreatment, respectively. One of these patients had a chemotherapy-refractory HPV-16+ squamous cell carcinoma. The other had a chemotherapy- and radiation-refractory HPV-18+ adenocarcinoma. Both patients demonstrated prolonged repopulation with HPV-reactive T-cells following treatment. Increased frequencies of HPV-specific T-cells were detectable after 6 months in one patient and after 13 months in the other. The 2 patients with HPV-reactive TIL who did not respond to treatment did not display repopulation with HPV-reactive T-cells.
Hinrichs concluded that infusion of HPV-TIL can engender durable, complete regression of metastatic cervical cancer in highly pretreated patients. Continued investigation of HPV-TIL for cervical cancer, and possibly other HPV-positive malignancies, is warranted.
1. Grupp SA, June CH. Adoptive cellular therapy. Curr Top Microbiol Immunol. 2011;344:149-172.
2. National Cancer Institute website. Cervical Cancer Treatment: PDQ®. Recurrent Cervical Cancer. Last modified: March 14, 2014. www.cancer.gov/cancertopics/pdq/treatment/cervical/HealthProfessional/page13. Accessed June 3, 2014.