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Interleukin 2 suppression of a murine bladder cancer implanted into kidney, bladder and skin; its organ specificity
K E Lee1, R W O'Donnell, G H Weiss
1Department of Urology, University of Rochester School of Medicine, New York.
Abstract:
Little is known about organ associated tumor response to systemic interleukin 2 (IL2) therapy. The effect of IL2 on bladder cancer growth in the skin and in the genitourinary tract was investigated. C3H mice were implanted with the syngeneic transitional cell carcinoma, MBT-2, intradermally (i.d.), beneath the left renal subcapsular area, and in one experiment, simultaneously in the bladder. IL2 (human recombinant form; Biogen Research Co) was given i.p. at 5000 U thrice daily for 5 consecutive days commencing on Day 3, or for 10 to 11 days commencing on Day 10 with some doses omitted at signs of toxicity. For comparison, mice bearing 3-d and 10-d tumors in the skin and subcapsular kidney were treated with chemotherapy (cisplatin, 6 mg./kg. X 3; mitomycin C, 3 mg./kg. X 3; cyclophosphamide, 75 mg./kg. X 1). IL2 therapy mediated growth suppression of 10-d tumors in the genitourinary organs and skin at a similar rate. In contrast to IL2, systemic chemotherapy mediated tumor suppression in an organ specific manner; renal subcapsular tumors responded to the chemotherapy, whereas i.d. tumors were insensitive. Three-day tumors (both i.d. and renal subcapsular tumor) responded relatively well to each treatment compared to 10-d tumors. These data suggest that in systemic immunotherapy with IL2, anatomic location of the tumor is less important for inducing an antitumor response than in chemotherapy.
Insights
Systemic interleukin 2 (IL2) therapy effectively suppresses tumor growth in various organs, unlike chemotherapy which shows organ-specific effects. Tumor age also influences treatment response in this study.
Area of Science:
- Immunotherapy
- Oncology
- Pharmacology
Background:
- Limited understanding of organ-specific tumor response to systemic interleukin 2 (IL2) therapy.
- Investigating the impact of IL2 on bladder cancer growth in different anatomical locations.
Purpose of the Study:
- To compare the efficacy of systemic IL2 therapy versus chemotherapy in treating tumors at various sites.
- To determine the influence of tumor location and age on treatment outcomes.
Main Methods:
- Syngeneic transitional cell carcinoma (MBT-2) implanted intradermally, beneath the renal capsule, and in the bladder of C3H mice.
- Treatment with systemic human recombinant IL2 or conventional chemotherapy agents (cisplatin, mitomycin C, cyclophosphamide).
- Evaluation of tumor growth suppression based on tumor age (3-day vs. 10-day) and anatomical location.
Main Results:
- IL2 therapy demonstrated similar growth suppression rates for 10-day tumors in both genitourinary organs and skin.
- Chemotherapy exhibited organ-specific effects, with renal tumors responding while dermal tumors did not.
- Both 3-day tumors, regardless of location, showed better responses to IL2 and chemotherapy compared to 10-day tumors.
Conclusions:
- Tumor anatomical location is less critical for IL2 immunotherapy response than for chemotherapy.
- Tumor age significantly impacts treatment efficacy for both IL2 and chemotherapy.
- These findings highlight distinct mechanisms of action between IL2 immunotherapy and conventional chemotherapy regarding tumor site and age.