Article Figures & Data
Figures
- Figure 1.
Clinical responses in patients after HPV-TIL therapy. A, Waterfall plot of the maximum change in the sum of target lesions, as compared with baseline measurements, in 29 patients. CR, complete response; PR, partial response; PD, progressive disease; +, stable disease. B, Spider plots of the change in the sum of target lesions from pretreatment baseline in 29 patients. Black circles (
) indicate ongoing responses; open squares () indicate PD due to either a new lesion(s) or increasing target or nontarget lesion(s). Black triangle () indicates PD in patient 24 with oropharyngeal cancer due to development of a new brain lesion after a PR of 5 months in duration. C and D, Contrast-enhanced CT scans obtained at baseline and after treatment for patient 24 with oropharyngeal cancer (C) and patient 26 with anal cancer (D). Tumors are marked by yellow arrows. Patient 24 had disease involving his left lung (first and second row) and mediastinum (third and fourth row). He experienced a PR of 5 months in duration due to a new brain lesion that was surgically excised. He was followed off-protocol, and his target lesions continued to regress, and there was no evidence of disease at most recent follow-up 51 months after treatment. Patient 26 had disease involving both lungs (first and second row). She experienced a PR of 4 months in duration due to increase in her target lesions. - Figure 2.
HPV reactivity of the infused T cells and peripheral blood T cells after infusion. A and B, Infused HPV-TILs to 27 patients with cervical and noncervical cancer with HPV16+ or HPV18+ tumors were assessed for reactivity against HPV type–specific E6 and E7 oncoproteins using CD137 upregulation by flow cytometry (A), and (IFNγ) production assays (B). The HPV-type of each patient's tumor is provided in Table 1. Patients 10 and 14 had non-HPV16+/18+ tumors and were not included in this analysis. Values shown represent sum of HPV-type–specific E6 and E7 reactivity after background subtraction (gp100). CD137 upregulation is depicted for CD3+ T cells. Data are representative of two independent experiments for patients 11 to 13 and 15 to 29, and one experiment for patients 1 to 9 due to unavailability of samples. C, Peripheral blood (PB) T cells from before and 1 month after treatment were assessed by IFNγ ELISA for reactivity against HPV-type–specific E6 and E7 oncoproteins in 22 patients (5 responding and 17 nonresponding patients). Patient numbers are indicated in the parentheses. Patients 1, 6, 16, 25, and 26 did not have available samples for this analysis. Patients 10 and 14 had non-HPV16+/18+ tumors and were not included in this analysis. Values shown represent sum of HPV-type–specific E6 and E7 spot-forming cells (SFC) after background subtraction (gp100). Eight of 22 patients had discernable HPV reactivity (>20 SFC after background subtraction). Data are representative of two independent experiments for patients 11–13, 15, 17–24, and 27–29, and one experiment for patients 2 to 5 and 7 to 9 due to unavailability of samples. CR, responding patient with a complete response; PR, responding patients with a partial response; NR, nonresponding patient.
Tables
- Table 1.
Characteristics of patients and administered T cells
Within CD3+ (%) Response Patient Age (years)/gender Histology HPV type Sites of disease Prior systemic treatment Cells (×109) CD4+ CD8+ No. of IL2 doses Type Duration or TTP (months) Cervical cancer 1 30/F ASC 18 Iliac lymph nodes, lung, lung hilum, retroperitoneum, vaginal cuff Cisplatin 101.4 29 72 7 PD 1 2 53/F SCC 18 Bone, liver, lung, lung hilum, mediastinum, pelvis Cisplatin, carboplatin, paclitaxel, topotecan, ixabepilone, dimethane sulfonate 126.0 10 90 3 PR 3 3 36/F SCC 16 Iliac lymph nodes, lung hilum, mediastinum, retroperitoneum Cisplatin, vincristine, bleomycin, gemcitabine, paclitaxel, topotecan 152.0 21 83 2 CR 67+ 4 55/F SCC 16 Axilla, breast, liver, omentum, pleura, soft tissue Cisplatin, carboplatin, paclitaxel, fluorouracil, irinotecan, dovitinib, pemetrexed 80.1 23 76 7 PD 2 5 44/F SCC 18 Brain, mediastinum, supraclavicular nodes Cisplatin 90.0 66 29 5 PD 2 6 36/F AC 18 Abdominal wall, liver surface, paracolic, pelvis, retroperitoneum Cisplatin 74.7 14 86 8 CR 53+ 7 59/F AC 18 Abdominal wall, lung Cisplatin, paclitaxel, carboplatin, bevacizumab 33.4 36 58 8 PD 1 8 31/F ASC 18 Pelvis, perihepatic mass Cisplatin, paclitaxel 46.1 64 29 9 PD 2 9 37/F AC 18 Axilla, bone, lung, mediastinum, pelvis, retroperitoneum Cisplatin, carboplatin, paclitaxel, ipilimumab 70.2 33 59 6 PD 1 10 39/F SCC not 16/18 Adrenal, retroperitoneum Cisplatin, paclitaxel, bevacizumab 100.0 8 92 5 PD 2 11 31/F SCC 16 Cervix, iliac lymph nodes, retroperitoneum Carboplatin, paclitaxel, bevacizumab 77.0 57 41 1 PD 2 12 48/F SCC 16 Bone, inguinal lymph nodes, lung, mediastinum, retroperitoneum Cisplatin, paclitaxel, bevacizumab, listeria-based vaccine trial 70.6 93 4 0 PR 3 13 30/F SCC 18 Cervix, inguinal lymph nodes, lung, mediastinum Cisplatin, brachytherapy 101.3 67 27 3 PD 3 14 49/F SCC not 16/18 Gastro-esophageal junction, mediastinum, retroperitoneum Cisplatin, carboplatin, paclitaxel, topotecan, bevacizumab 68.8 53 41 2 PD 2 15 61/F AC 16 Bone, inguinal lymph nodes, lung Carboplatin, docetaxel, cisplatin, topotecan, ifosfamide, adriamycin, etoposide 73.9 84 16 1 PD 3 16 51/F SCC 18 Liver, pelvic, peripancreatic, spleen Cisplatin, gemcitabine, carboplatin, paclitaxel, bevacizumab 115 71 29 0 PD 2 17 63/F SCC 18 Lung, lung hilum Cisplatin, carboplatin, paclitaxel, bevacizumab 112.0 78 22 4 PD 5 18 35/F NE 18 Lung, lung hilum, liver Cisplatin, etoposide, topotecan, paclitaxel, bevacizumab 9.0 67 34 3 PR 3 Noncervical cancer 19 55/M Tonsillar SCC 16 Axilla, lung, subcutaneous tissue Cisplatin, fluorouracil, taxotere, carboplatin, cetuximab 89.1 96 2 1 PD 2 20 60/M Head/neck SCC 16 Axilla, bone, liver, peripancreatic, periportal lymph node, pleura Cisplatin, capecitabine, carboplatin 150.0 29 64 6 PD 2 21 58/F Anal SCC 16 Lung, mediastinum, pleura Cisplatin, fluorouracil, carboplatin, paclitaxel, cetuximab, irinotecan 31.5 47 50 2 PD 3 22 50/F Anal SCC 16 Mediastinum, retroperitoneum Cisplatin, fluorouracil, mitomycin C, paclitaxel, carboplatin 69.0 75 16 5 PD 8 23 58/F Anal SCC 16 Iliac lymph nodes, liver, retroperitoneum Cisplatin, fluorouracil, mitomycin C 47.5 86 9 1 PD 2 24 60/M Tonsillar SCC 16 Lung, mediastinum Cisplatin, docetaxel, bevacizumab, cetuximab, fluorouracil, gemcitabine 130.9 41 51 3 PR 5 25 49/F Anal SCC 16 Pleura Cisplatin, fluorouracil, rigosertib, capecitabine 133.0 67 20 5 PD 2 26 48/F Anal SCC 16 Lung Cisplatin, fluorouracil, mitomycin C, capecitabine 18.4 47 50 5 PR 4 27 52/M Head/neck SCC 16 Axilla, chest wall, lung hilum, mediastinum, subcutaneous tissue Cisplatin, fluorouracil, taxotere 125.0 97 3 5 PD 2 28 60/M Head/neck SCC 16 Lung, lung hilum, mediastinum, para-aortic lymph node, pleura Cisplatin, carboplatin, fluorouracil, cetuximab, pembrolizumab 102.0 6 94 4 PD 3 29 56/F Vaginal AC 16 Lung, lung hilum, scapula, para-spinal Cisplatin, paclitaxel, carboplatin, pemetrexed 107.0 46 55 5 PD 4 Abbreviations: AC, adenocarcinoma; ASC, adenosquamous cell carcinoma; F, female; M, male; NE, neuroendocrine; SCC, squamous cell carcinoma; TTP, time to progression.
- Table 2.
Adverse events (grades 3 and 4)
Adverse event No. of patients (#) Lymphopenia 29 Neutropenia 29 Thrombocytopenia 29 Anemia 25 Infectiona 17 Febrile neutropenia 12 Metabolic disorders 12 Hypoxia 8 Nausea/vomiting 6 Dyspnea 4 Diarrhea 3 Fatigue 3 Hypotension 3 Cystitis 2 Hemorrhageb 2 Oliguria 2 Renal failurec 2 Syncope 2 Ureteral obstructiond 2 Dysphagia 1 Confusion 1
Supplementary Data
- Supplementary Data - Figures for data supplement
- Supplementary Data - Text for data supplement
Volume 25, Issue 5
