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Polyinosinic-Polycytidylic Acid Complexed with Poly-L-lysine and Carboxymethylcellulose in Combination with Interleukin 2 in Patients with Cancer: Clinical and Immunological Effects¹

Clinical Services Program, Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research Development Center, Frederick, Maryland 21702 [C. H. E., W. J. U., W. C. K., J. L. R., J. M. B.]; Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, Frederick, Maryland 21701 [R. G. S., D. L. L., S. P. C., J. W. S.]; Frederick Memorial Hospital, Frederick, Maryland 21701 [M. J. J.]; Immunomedics, Inc., Warren, New Jersey 07060 [C. M. P.]; and Data Management Services, Inc., National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [K. L. M., W. G. A.]

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 10⁶ 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 (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 or 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.

¹ This research was sponsored, at least in part, by the National Cancer Institute, DHHS, under Contract N01-CO-74102 with Program Resources, Inc./DynCorp. The contents of this publication do not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.

² To whom requests for reprints should be addressed, at Clinical Services Program, Program Resources, Inc./DynCorp, NCI-FCRDC, P. O. Box B, Frederick, MD 21702-1201.

Received 11/26/91. Accepted 3/19/92.