Improved expansion, functionality and tumor targeting of adoptively transferred T cells with kinetically engineered IL-2

The adoptive transfer of cancer-specific T cells in combination with high dose interleukin-2 (IL-2) is able to induce effective anti-tumor responses. However, tumors frequently relapse after an initial response and the known toxicities of IL-2 further limit the use of this therapy. NKTR-214 is a CD122-biased polyethylene glycol (PEG)-genetically engineered IL-2 designed to provide sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2Rβγ) to preferentially activate and expand CD8 T and natural killer (NK) cells over T regulatory cells (Tregs) in the tumor. We report that combination of adoptive T cell transfer (ACT) and NKTR-214 markedly increases the proliferation, homing and polyfunctionality of antitumor T cells into the tumor. The treatment is well tolerated and leads to robust anti-tumor response in the aggressive B16F10 model. These results suggest that NKTR-214 could improve the efficacy of ACT protocols tested in humans. C57/BL6 mice were implanted subcutaneously with B16F10 syngeneic murine melanoma cell line. When the tumors reached the volume of at least 150mm3, mice received adoptive cell transfer of pmel-1 T cells with NKTR-214 or IL-2. Tumors from three biological replicates were harvested at day 12 after treatment .