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.