This therapy, which has been invented by Professor Wu Nianceng in our hospital, is special for treatment of malignant glioma.
BACKGROUND and PRINCIPLE
The survival rate for malignant glioma remains dismal. Extensive surgical resections, radiotherapy with or without radiosensitizers, and various chemotherapy regimens have shown little impact on survival, which ranged from 14 to 60 weeks with 18-survivorship from 0% to 37 percent. This has stimulated work to identify additional therapeutic modalities that might improve prognosis.
Immunotherapy addresses anarea of demonstrated deficiency in patients with primary brain tumors, in whom numerous defects of cellular immunity have been discovered, including impaired delayed hypersensitivity for common recall and autologous tumor antigens, a decrease in circulating T-lymphocytes, shifts in lymphocyte subpopulation in peripheral blood, incomplete responseof peripheral blood lymphocytes to intrleukin-2,decreased mitogen-induced blastogenesis, which may affect the host’s ability to halt neoplastic growth. Surgery, radiotherapy, and chemotherapy also debilitate the immune system of patients with brain tumor. The tumors themselves have direct immunosuppressive effects via expression of suppressor factors, such as transforming growth factor-beta.
Based on above data, professor Wu has studied the effects of local administration of a special immunomodulator—S311 on glioma and invented a therapy called local immunotherapy in tumor bed for treatment and prevention of glioma.
PROCEDURE
Patients received routine surgical removal of tumor tissue visible as much as possible and then were given implantation of Ommiya capsule in tumor bed. The open end of the capsule was implanted in cavity of tumor and the closed end was put under the cranial skin. Postoperatively, from the fifth-seventh day, S311 was percutaneously infused into Ommiya capsule, 2mg per session, once every 2 days, for 5 session as a course. Afterward, a course of treatment was given every one month for 3 courses and then a course every 3 months for 3 courses, and again, a course every 12 months for longer duration as long as possible. S311, a sterile suspension of 2 mg RNA per vial in a tris-megnesium buffer stored frozen at –20°C, was obtained from Immunology Research Section of Navy Institute of Medicine (Shanghai).
CLINICAL APPLICATION AND RESULTS
- 45 patients who received this therapy from 1996 to 1997, had survival time of from 9 to 81 months with median of 38.5 months, and had overall survival rates of 96.2%, 86.7%, 79.0%, 74.28%, 61.5%, 55.5% and 50.0%,respectively, at 1,2,3,4,5,6 and 7 years. Of 31 patients who are alive, 28 cases have disease-free survival, and 3 cases have presence of tumor on CT or MRI but tumor’s volume remains stable. Of 14 patients died, 9 died of tumor recurrence, and 5 died of non-tumor causes. Of 4 patients died after fourth year following the therapy, 3 died of non-tumor causes. Apart of transient fever, no serious adverse reaction was noted.
- These results were better than results of studies reported using the multimodality therapy (surgery, radiotherapy, chemotherapy), in which median survival time ranged from 10 to 14 months.
- From Jun 2002 to now, there are more 100 patients with glioma who have received this therapy with better results.
COMMENT
WHY his therapy can get a superior efficacy for glioma? May be because following considerations:
- S311 is a biologic response modifier consisting of sized membrane vesicles and ribosomes derived from preparation ofSerratia marcescens, has been shown to augment the activity of human natural-killer (NK) cellagainst tumor cells in vitro and to stimulate cytotoxity in the peripheral-blood mononuclear cells of patients, in whom this activity has been downregulated. NK-cell cytotoxicity was increased three to 10-fold within 24 hours of S311 injection. Also, it was proved that S311’s action appears to be via triggering of interferon-gamma production through binding of the low affinity immunoglobulin G Fc fragment receptor (type Ⅲ, CD 16), by acting in combination with interleukin-2 to produce synergistically enhanced cytotoxity, and by direct contrasuppressor activity in the face of down-regulated cytotoxity in patients with impaired immunity.
- Wu has used a special route of administration of the drug, and S311 was given infusion into tumor bed through implanted Ommiyo capsule. The modification was based on the following reasons:
- Local administration may eliminate the effect of blood-brain-barrier (BBB) and blood-tumor-barrier (BTB), which reduce delivery of lipid-soluble drugs into brain tumor;
- The recurrence of glioma mainly occurs in local area of residual tumor in brain, and
- The presence of partial immune competence in situ of tumor, including intratumoral lymphocytic infiltrates mainly composed of CD8+ cells, NK cells and macrophage, was noted, despite of immunodeficiencies. These factsimply that modulation or increase oflocal immune can bring about total removal of residual tumor.
ADVERSE EFFECTS
There was no significant complication apart from transient fever in the initiative sessions.
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