Immunotherapy with effector cells and IL-2 of lymph node metastases of human squamous-cell carcinoma of the head and neck established in nude mice.
We have previously reported that immune anti-tumor effector cells, both cytotoxic T lymphocytes (CTLs) and IL-2-activated natural killer (A-NK) cells, are effective at eliminating human head-and-neck cancer (HNC) targets in vitro and in vivo in xenograft models. In this study, these 2 types of human effector cell were compared for the ability to prevent the development of lymph node metastases in a metastasis model of human squamous-cell carcinoma of the head and neck (SCCHN) established in nude mice. A tumor cell line, OSC-19, was injected into the floor of the mouth in nude mice, and the tumor grew progressively and metastasized to cervical lymph nodes by day 21. As effector cells, a human HLA-A2-restricted CTL line recognizing a shared antigen on OSC-19 and human non-MHC-restricted A-NK cells were used. Both types of effector cell mediated high levels of lysis against OSC-19 targets in 4-hr (51)Cr-release assays. Administration of human CTLs or A-NK cells and IL-2 to the site of tumor growth in mice with 7-day OSC-19 tumors resulted in significant reduction of the number of lymph node metastases relative to untreated or sham-operated controls or to mice treated with IL-2 without the effector cells. Our results suggest that in a xenograft model of human SCCHN implanted in the oral cavity of nude mice, the development of lymph node metastases can be successfully controlled by adoptive transfer of human SCCHN-specific CTLs or SCCHN-reactive A-NK cells plus IL-2.
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
K
K
Chikamatsu
T E
TE
Reichert
Y
Y
Kashii
T
T
Saito
S
S
Kawashiri
E
E
Yamamoto
T L
TL
Whiteside
D000818:Animals; D001835:Body Weight; D002294:Carcinoma, Squamous Cell / Q000556:secondary / Q000628:therapy*; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015979:Killer Cells, Lymphokine-Activated / Q000637:transplantation*; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000473:pathology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000637:transplantation*