Development and therapeutic effect of adoptively transferred T cells primed by tumor lysate-pulsed autologous dendritic cells in a patient with metastatic endometrial cancer.
We describe a 65-year-old woman with a large surgically unresectable and chemoresistant liver metastasis of endometrial carcinoma who was treated by infusion with peripheral blood T cells stimulated with tumor lysate-pulsed autologous dendritic cells (DC). Extensive in vitro characterization of the DC-activated T cells included phenotypic analysis, cytotoxicity, and intracellular cytokine secretion. High cytotoxicity was observed against autologous tumor cells, but not against NK-sensitive K562 cells, autologous Con-A lymphoblasts, or autologous Epstein-Barr virus-transformed lymphoblastoid cells. Blocking studies demonstrated that lytic activity was HLA class I restricted. Two-color flow cytometric analysis revealed that a significant proportion of CD8+ T cells was also CD56+, and analysis of intracellular IFN-gamma and IL-4 expression suggested a type 1 cytokine bias. The patient was treated by three infusions of tumor-specific T cells at 3- to 4-week intervals, and in vivo distribution of the T cells was followed by (111)In oxine labeling and serial gamma camera imaging. Tumor localization and accumulation of labeled lymphocytes was consistently detected at serial time points following each injection. However, deep infiltration of the large tumor mass by activated T cells was minimal, as evaluated in 3 dimensions by single photon emission computerized tomography (SPECT) imaging. Transient serum increases of the tumor marker lactate dehydrogenase (LDH), were detectable after each injection. Similar posttreatment elevations were seen for serum uric acid and potassium. Clinically, stabilization of the large liver metastasis was obtained during treatment. Collectively, these results indicate that tumor-specific CD8+ cytotoxic T-cell responses can be generated in patients with endometrial cancer, and suggest that T-cell immunotherapy may be of therapeutic value in patients harboring metastatic disease.
Santin
A D
AD
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Arkansas, Little Rock, Ark., USA.
Hermonat
P L
PL
Ravaggi
A
A
Bellone
S
S
Cowan
C
C
Coke
C
C
Pecorelli
S
S
Cannon
M J
MJ
Parham
G P
GP
D000368:Aged; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D016889:Endometrial Neoplasms / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D006499:Hepatic Artery; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008113:Liver Neoplasms / Q000532:radiotherapy / Q000556:secondary* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014057:Tomography, X-Ray Computed; D014527:Uric Acid / Q000097:blood
D019002:CD56 Antigen; D015395:Histocompatibility Antigens Class I; D014527:Uric Acid; D007770:L-Lactate Dehydrogenase