Adoptive cellular immunotherapy for the treatment of malignant gliomas

The median survival for adults with recurrent primary malignant gliomas is 56 weeks following surgery, radiation, and chemotherapy. Generally, reopera tion can extend the median survival an additional 26-32 weeks. We have deve loped an aggressive treatment program that utilizes low doses of interleuki n-2 (IL-2) combined with ex vivo activated killer cells (LAK) infused via a n indwelling catheter placed into the surgical resection cavity. Autologous leukocytes were collected during a standard 3-4 h outpatient leukapheresis procedure, then activated ex vivo for 4-5 days with high doses of IL-2. Th e treatment protocol consisted of two 2-week cycles of therapy over a 6-wee k period. Patients with stable disease or objective response on follow-up M RI scans were retreated at 3-month intervals. Acute and cumulative IL-2-rel ated toxicities were observed, but limited, and included fever, headache an d transient neurologic irritation. Corticosteroid levels and usage were str ictly controlled during immunotherapy, although higher doses were used inte rmittently to mitigate toxicity. Biologic changes included lymphocytic infi ltration, regional eosinophilia, tumor necrosis, and the localized producti on of IL-2, IFN-gamma and IL-12, demonstrated by in situ hybridization and immunohistochemistry. Summary IL-2 plus autogeneic LAK cells can be safely administered intracavitary to treat high grade primary brain tumors with li mited toxicity within the central nervous system. Six out of 28 patients ha d long-term survival of greater than 2 years post-reoperation plus immunoth erapy with 2 patients alive over 8 years. The presence of a marked regional eosinophilia appeared to correlate with increased survival and may be pred ictive of a biologic and therapeutic response. Regional adoptive immune the rapy was well tolerated and should be considered an option for patients wit h high-grade tumors refractive to standard therapeutic approaches. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.