Murine studies using polyethylene glycol-modified recombinant human interleukin 2 (PEG-IL-2): antitumor effects of PEG-IL2 alone and in combination with adoptive cellular transfer.
A polyethylene glycol-modified form of recombinant human IL-2 (PEG-IL-2) was tested for murine antitumor effects in vitro and in vivo. This PEG-IL-2 was demonstrated to retain the in vitro ability to support T cell proliferation, enhance a mixed lymphocyte reaction, and generate lymphokine-activated killer (LAK) cells. It was found to have a circulating half-life in mice 25 times longer than unmodified recombinant IL-2 (RIL-2). Serum levels were detected up to 60 h after a single intravenous injection. When given as a single, intravenous administration the antitumor effect of this material was similar to multiple, repeated bolus doses of RIL-2. PEG-IL-2 was also found to support the in vivo efficacy of adoptively transferred LAK cells and tumor infiltrating lymphocytes (TIL). Using a congenic TIL (Thy 1.1), persistence of adoptively transferred TIL was found to be prolonged with PEG-IL-2 compared to repeated boluses of RIL-2. Four days after transfer, twice as many Thy 1.1 TIL were recoverable from the lungs of mice given PEG-IL-2. These studies show that PEG-IL-2 is a modified lymphokine with significant antitumor activity in murine systems and is superior to bolus RIL-2 in enhancing the survival of adoptively transferred TIL.
Yang
J C
JC
Surgery Branch, National Cancer Institute, Bethesda, MD 20892.
Schwarz
S L
SL
Perry-Lalley
D M
DM
Rosenberg
S A
SA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016219:Immunotherapy, Adoptive; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D008175:Lung Neoplasms / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000627:therapeutic use; D012016:Reference Values
D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; C067245:interleukin-2, polyethylene glycol-modified; D011092:Polyethylene Glycols