Immunotherapy of murine sarcomas using lymphokine activated killer cells: optimization of the schedule and route of administration of recombinant interleukin-2
Interleukin-2 (IL-2) at high doses or at low doses in concert with lymphokine-activated killer (LAK) cells can produce regression of established pulmonary and hepatic metastases from a variety of tumors in mice. IL-2 appears to mediate its antitumor effect through the generation of LAK cells in vivo from endogenous lymphocytes and by the stimulation of host and transferred LAK cell proliferation in tissues. In this paper we have investigated different strategies for IL-2 administration to determine which regimen produced maximal in vivo proliferation and optimal immunotherapeutic efficacy of LAK cells. Tissue expansion of lymphoid cells was assessed using an assay of in vivo labeling of dividing cells by the thymidine analogue, 5-(/sup 125/I)iododeoxyuridine. The therapeutic effect of the different IL-2 administration protocols was determined by evaluating their efficacy in the treatment of established, 3-day pulmonary metastases from sarcomas in mice. The selection of IL-2 injection regimens for evaluation was based upon pharmacokinetic studies of IL-2 in mice. A single i.v. or i.p. dose yielded high peak IL-2 levels that could be measured for only a few hours after injection, while IL-2 given i.p. thrice daily produced titers that were detectable throughout the study periods (greater than or equal to 6 units/ml of serum after 100,000 units of IL-2 i.p. thrice daily). Using the proliferation and therapy models, we tested the same cumulative daily doses of IL-2 administered by i.v. or i.p. once daily, or i.p. thrice daily regimens. The i.p. thrice daily protocol stimulated greater lymphoid cell proliferation in the lungs, for example, than did the other regimens.
- Research Organization:
- National Cancer Institute, Bethesda, MD
- OSTI ID:
- 5559978
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 6; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AZINES
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DEOXYURIDINE
DIGESTIVE SYSTEM
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
GLANDS
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMMUNOTHERAPY
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LIVER
LUNGS
LYMPHOCYTES
LYMPHOKINES
MAMMALS
MATERIALS
METASTASES
MICE
MITOGENS
NEOPLASMS
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RESPIRATORY SYSTEM
RIBOSIDES
RODENTS
SARCOMAS
SOMATIC CELLS
THERAPY
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URACILS
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