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

A prospective pilot study was performed in order to assess the safety of tr eating recurrent malignant gliomas (MGs) with locally infused autologous tu mor infiltrating lymphocytes (TILs) and recombinant interleukin-2, (rIL-2). Six patients were entered between June 27, 1994 and June 2, 1995 and follo wed until July 1, 1998. At surgery an Ommaya reservoir was placed for later infusion of TILs and rIL-2. Following surgery, autologous TILs were expand ed 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 m onth. Following completion of immunotherapy all patients were offered chemo therapy. Phenotypic analysis demonstrated TILs to be T-lymphocytes (87-99% CD3+). Of these, 4 of 6 cases (67%) phenotyped as cytotoxic/suppressor T-ly mphocytes (CD8+) and 2 of 6 cases (33%) phenotyped as helper/inducer T-lymp hocytes (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 develop ed 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 respons e, 2 demonstrated stable disease and 1 patient progressed. At long term fol low-up, 1 patient had a complete response (45 month follow-up), 2 had a par tial response (48 and 47 month follow-up) and 3 patients expired as a resul t of progressive disease (at 12, 12 and 18 months following immunotherapy). A relationship between subsequent chemotherapy or extent of resection to o utcome 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 indicate d to determine the safety and long term efficacy of TIL immunotherapy.