Local adoptive immunotherapy of human head and neck cancer xenografts in nude mice with lymphokine-activated killer cells and interleukin 2.
The efficacy of local adoptive immunotherapy with human lymphokine-activated killer cells and recombinant interleukin 2 (rIL-2) in growth inhibition of established squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a nude mouse model. The model of xenografted SCCHN was established by s.c. injections of in vitro maintained tumor cells (2-10 x 10(6) cells/mouse) into the flank of splenectomized animals pretreated with cyclophosphamide (200 mg/kg). The SCCHN line used was tumorigenic in 95% of the appropriately conditioned nude mice. Inhibition of tumor growth by locally administered effector cells was the end point of the study, since the tumors did not metastasize within 6 weeks of tumor challenge. Either i.p. or local administration of rIL-2 alone (1000 units/day) to the tumor site daily for 2 weeks resulted in a significant inhibition of tumor growth. In the absence of detectable natural killer activity in these mice, a modest dose of rIL-2 had a direct antitumor effect on SCCHN cells in vivo. In addition, complete inhibition of tumor growth was achieved with 3 times weekly injections of 5-10 x 10(6) lymphokine-activated killer cells delivered to the tumor site and 1000 units of rIL-2 administered locally every day for 2 weeks. Our data indicate that local or systemic immunotherapy with rIL-2 alone or local adoptive immunotherapy with an adequate dose of lymphokine-activated killer cells plus rIL-2 may be effective in preventing the growth of established SCCHN tumors in vivo.
Sacchi
M
M
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Snyderman
C H
CH
Heo
D S
DS
Johnson
J T
JT
d'Amico
F
F
Herberman
R B
RB
Whiteside
T L
TL
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007116:Immunization, Passive; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation
D015703:Antigens, CD; D007376:Interleukin-2