Effective immunotherapy with local low doses of interleukin-2.
IL-2 treatment for metastatic tumors in man is usually given systemically with high doses, often in conjunction with large numbers of LAK-cells. Complete tumor regression is obtained in less than 10%, this treatment causes severe toxicity, and culturing of LAK-cells is laborious and expensive. In this paper we demonstrate that small amounts of locally applied rIL-2 alone, if given at the right time, can cure about 70% of DBA/2 mice with large metastasized syngeneic SL2 lymphoma comprising 4-10% of the total body weight, a tumor load hitherto considered fatal. Moreover, 3 out of 5 cows with ocular squamous cell carcinoma (BOSCC) of 1 x 1 up to 3 x 4 cm were cured with low doses of rIL-2 only. Taken together, we have now tested 11 tumors in animals. No antitumor effect was observed in EL4 lymphoma in C57BL mice. Partial antitumor effects were detected in RBL5 lymphoma in C57BL mice, stomach carcinoma in BALB/c mice, MOT-carcinoma in C3H mice, liver carcinoma in guinea pigs and bovine vulval papilloma/carcinoma. Complete tumor regression was obtained in SL2 lymphoma, L5178Y lymphoma, L1210 lymphoma, and P815 mastocytoma in DBA/2 mice and in bovine ocular squamous cell carcinoma. Low doses of locally injected IL-2 induce systemic immunity, as shown in DBA/2 mice bearing syngeneic SL2 lymphoma cells. We conclude that local low dose treatment can be effective and results in a high cure rate in several tumor models. In the DBA/2-SL2 lymphoma model this treatment is 100-1000 times more effective than any form of immunotherapy we have tested during 20 years in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
Den Otter
W
W
Department of Pathology, University Hospital Utrecht, The Netherlands.
Maas
R A
RA
Koten
J W
JW
Dullens
H F
HF
Bernsen
M
M
Klein
W R
WR
Rutten
V P
VP
Steerenberg
P A
PA
Balemans
L
L
Ruitenberg
E J
EJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D002417:Cattle; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008223:Lymphoma / Q000628:therapy; D051379:Mice; D008811:Mice, Inbred DBA; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage
D007376:Interleukin-2; D011994:Recombinant Proteins