Glioblastoma multiform is one of the most invasive and deadly cancers that progresses rapidly and leads to death. Surgery with radiotherapy /chemotherapy, as a treatment approach is ineffective in some cases and is associated with relapse and death. Immunotherapy is a special strategy that used as an adjunct therapy in various cancers and among the various methods of immunotherapy; it seems that cell therapy with NK cells is of special importance. A previous study conducted at the Royan Research Institute showed that NK cell proliferation and amplification resulted in the removal of glioblastoma tumor masses in the animal model. The animals had no evidence of tumor recurrence after treatment, and all tumor-related complications resolved after treatment. Therefore, in this study, the investigators intend to evaluate the safety of ex vivo activated cells in 5 patients with glioblastoma multiform whose disease has returned after treatment and who have not had any appropriate treatment.

1- patient selection 2- leukapheresis 3- CD56+ cells isolation 4- NK cells activation 5- assessment of functionality and purity 6- quality control tests 7-NK cell injection in tumor cavity.

Age: 3-60 Year -

• Sex: Both
• Lansky performance scale/Karnofsky performance scale: 70-100%
• Life span expectation: >6 months
• Hemoglobin: > 10.0 g/dl
• Platelet count > 100,000/mm³
• Serum total bilirubin < 1.5 times upper limit of normal (ULN)
• ALT and AST < 2.5 times ULN
• Serum creatinine < 1.5 times ULN
• No diagnosis of any other invasive cancer within the past 5 years.
• No concurrent serious medical or psychiatric illness that may interfere with giving informed consent or conducting this study

Exclusion Criteria:

• Patients whose MRI and MRS images is in favor of radio necrosis.
• Due to emergency conditions, the patient cannot tolerate the new treatment
• Lack of a suitable donor or insufficient number of NK cells.
• Development of a new neurological defect after the first injection
• Patient death during surgery
• Closing the reservoir for the next injection (if this problem is resolved, the injections will be done again).