Document Detail


Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects.
MedLine Citation:
PMID:  1591717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment.
Authors:
C H Ewel; W J Urba; W C Kopp; J W Smith; R G Steis; J L Rossio; D L Longo; M J Jones; W G Alvord; C M Pinsky
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  52     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1992 Jun 
Date Detail:
Created Date:  1992-06-30     Completed Date:  1992-06-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3005-10     Citation Subset:  IM    
Affiliation:
Clinical Services Program, Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research Development Center, Maryland 21702.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / analysis
Biopterin / analogs & derivatives,  blood
Carboxymethylcellulose / therapeutic use,  toxicity*
Cytotoxicity, Immunologic
Drug Evaluation
Female
Humans
Interleukin-2 / therapeutic use,  toxicity*
Killer Cells, Natural / immunology
Male
Middle Aged
Neoplasms / immunology,  therapy*
Neopterin
Poly I-C / therapeutic use,  toxicity*
Polylysine / therapeutic use,  toxicity*
Grant Support
ID/Acronym/Agency:
N01-CO-74102/CO/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Interleukin-2; 22150-76-1/Biopterin; 24939-03-5/Poly I-C; 25104-18-1/Polylysine; 59789-29-6/poly ICLC; 670-65-5/Neopterin; 9004-32-4/Carboxymethylcellulose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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