Thirteen patients with recurrent glioblastoma were treated with adoptively transferred autologous lymphokine activated killer (LAK) cells and recombinant interleukin-2 (rIL-2). Patients' blood mononuclear cells (MNC) obtained by leukapheresis were cultured at 2.5 million MNC per ml for 3 to 5 days in media containing 1000 U rIL-2/ml. After incubation, the nonadherent MNC from all cultures (0.5-5 X lo9) were combined and concentrated for infusion in 5 to 10 ml saline containing lo6 U rIL-2. Nine patients received one injection of LAK cells and rIL-2 into the brain tissue immediately surrounding the tumor cavity during craniotomy for subtotal tumor removal (Group 1). On each of the 3 days after surgery, patients received boosters of lo6 U rIL-2 delivered into the tumor cavity through a skin flap or via an Ommaya reservoir. Approximately 1 to 2 weeks after this series of injections, these patients were treated with a second cycle of LAK cells and rIL-2 injected into the tumor cavity using the reservoir. Four patients received both adoptive immunotherapy cycles by intracavitary injection (Group 2). In this relatively small patient pool, neither age, sex, Karnofsky score, treatment history, nor anticonvulsant and steroid dosage appeared to influence a patient's ability to make LAK cells. The therapy, itself, was well-tolerated by all patients although they all displayed symptoms of aseptic meningitis and increased intracranial pressure, Le., headache, fever, malaise on the days of LAK cell and/or rIL-2 infusion. The therapy did not appear to have a significant impact on patient survival (mean, 30 weeks) especially for those patients with a high postsurgical tumor burden. As the therapy is safe, the authors believe its efficacy can best be tested in patients with a newly diagnosed or recurrent glioblastoma which lies in an area where a near-total resection is possible.
Cancer 62:665-671,1988. HE EARLY FINDINGS of Ridley and Cavanaugh' and T other^^-^ that survival with glioblastoma correlated with the degree of lymphocytic infiltration seen in the tumor spawned the development and testing of a variety of immunotherapeutic approaches for the treatment of this tumor (reviewed by Apuzzo and Mitchell6). Over 10 years ago, we conducted a clinical trial with recurrent glioma patients treated with autologous leukocyte infusions into the tumor bed or cystic cavity via indwelling catheter^.^ Infusions of 50 million to 1.5 billion bum From the Departments of *Anatomy and ?Surgery, Division of Neurosurgery, Virginia Commonwealth University, Medical College of Virginia, Richmond.
Supported in part by grants from the NIH, NS2 13 13, and the Jeffress Memorial Trust.
The authors thank the neurosurgery residents and nurses who have participated in the care of our patients. The authors also thank Doctor Sallie Cook, Director of the MCV Blood Bank, and nurses of the Leukapheresis Unit for their assistance.