Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas

Abstract

A prospective pilot study was performed in order to assess the safety of treating recurrent malignant gliomas (MGs) with locally infused autologous tumor infiltrating lymphocytes (TILs) and recombinant interleukin-2 (rIL-2). Six patients were entered between June 27, 1994 and June 2, 1995 and followed until July 1, 1998. At surgery an Ommaya reservoir was placed for later infusion of TILs and rIL-2. Following surgery, autologous TILs were expanded in vitro in the presence of rIL-2 and infused on treatment days 1 and 14, with concurrent rIL-2 infusions performed three times each week for one month. Following completion of immunotherapy all patients were offered chemotherapy. Phenotypic analysis demonstrated TILs to be T-lymphocytes (87-99% CD3+). Of these, 4 of 6 cases (67%) phenotyped as cytotoxic/suppressor T-lymphocytes (CD8+) and 2 of 6 cases (33%) phenotyped as helper/inducer T-lymphocytes (CD4+). TILs demonstrated limited selective cytotoxicity, with dose dependent cytotoxicity against autologous tumor, allogenic tumor and long term MG cell lines. There were no significant (Grade 3 or 4) complications. One patient developed transient low grade fevers, and 2 developed asymptomatic hydrocephalus. All patients developed transient and asymptomatic cerebral swelling, noted on the immediate post-treatment imaging studies. At three and six month follow-up, 3 patients responded with partial response, 2 demonstrated stable disease and 1 patient progressed. At long term follow-up, 1 patient had a complete response (45 month follow-up), 2 had a partial response (48 and 47 month follow-up) and 3 patients expired as a result of progressive disease (at 12, 12 and 18 months following immunotherapy). A relationship between subsequent chemotherapy or extent of resection to outcome was not apparent but could not be excluded. This pilot study demonstrated that locally infused autologous TILs and rIL-2 could be delivered without serious toxicity. Further studies are indicated to determine the safety and long term efficacy of TIL immunotherapy.