TREATMENT OF RECURRENT GLIOMA WITH INTRACAVITARY ALLOREACTIVE CYTOTOXIC T-LYMPHOCYTES AND INTERLEUKIN-2

For a single-dose toxicity assessment, five patients with recurrent ma lignant glioma (ages 29-46 years) were treated with intracavitary allo reactive cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2). The t rial tested the hypothesis that alloreactive CTL, sensitized to the ma jor histocompatibility complex (MHC) proteins of the patient, offer se lective, targeted killing of glioma cells that express MHC. Patient ly mphocytes, which also express MHC, were irradiated and placed into Cel lMax artificial capillary systems with lymphocytes from MHC-disparate donors and CTL developed over a 2- to 3-week period with a low concent ration of IL-2. The CTL largely expressed CD3 and CD11a/CD8 markers an d lysed targets displaying patient MHC. CTL were implanted into the tu mor bed at surgery and a catheter was used for subsequent infusions. P atients received one to five treatment cycles every other month; one c ycle generally consisted of two or three CTL infusates administered wi thin a 1- to 2-week period. Different unrelated donors were used for e ach cycle. Treatment was well tolerated; transient toxicity at grades 1-3 was recorded by NCI Common Toxicity Scale criteria. Two glioblasto ma patients have died; one from tumor recurrence locally and the other from recurrence at a site distant from the treatment. Two of the five patients completed five cycles; one anaplastic oligodendroglioma pati ent shows no evidence of tumor 30 months from the start of immune ther apy and an anaplastic astrocytoma patient shows stable disease 28 mont hs after initiation of therapy. One anaplastic oligodendroglioma patie nt, who dropped the protocol during her second treatment cycle, has no evidence of tumor 28 months after recurrence.