Long-term immunological memory in the resistance of rats to transplanted intracerebral 9L gliosarcoma (9LGS) following subcutaneous immunization with9LGS cells

Glioblastoma multiforme (GBM) is the most common primary human brain tumor. About 7000 new cases are diagnosed yearly in the USA. Despite current neur osurgical and postoperative radiotherapeutic tumor cytoreduction methods, i n most cases occult foci of tumor cells infiltrate surrounding edematous br ain tissues and cause recurrent disease within one year. GEM is almost inva riably fatal within a few years after it is diagnosed. Our goal is to achie ve long-term control of GEM by combining immunoprophylaxis with a radiation -based technique, such as boron neutron-capture therapy (BNCT), potentially capable of specifically targeting the infiltrating tumor cells while spari ng the surrounding normal brain tissue. It has long been known that the subcutaneous (sc) injection of irradiated c ells or untreated cultured cells (and the removal of the resulting tumors) derived from the well characterized, highly immunogenic 9L gliosarcoma (9LG S) rat model into young isogenic rats can prevent tumor growth after subseq uent sc or intracranial (ic) injection of untreated, otherwise lethal 9LGS cells. In this study we have confirmed, quantified and extended those findi ngs to study the efficacy of such immunological memory in normal aging rats and in aging rats previously treated for ic 9LGS tumors by BNCT. (1) The s c injection of 5,000,000 untreated 9LGS cells and the surgical removal of t he resulting tumors (method A) protected 80% of normal young rats from an i c challenge with 10,000 untreated 9LGS cells, and a single sc injection of 5,000,000 lethally X-irradiated 9LGS cells (method B) protected 66% of them , but multiple sc injections with a crude particulate fraction prepared fro m 9LGS cells were not protective. Protection is long-lasting since contrala teral ic rechallenge of six-month survivors with an injection of 10,000 via ble 9LGS cells resulted in 100% survival. (2) Normal one-year-old rats were only slightly less protected than were normal young rats, similar to 70% r ather than similar to 80% (method A) and similar to 60% rather than - 66% ( method B). (3) BNCT treatment alone resulted in partial immunological prote ction, as 30% of one-year post-BNCT survivors of ic 9LGS tumors prevailed a fter contralateral ic rechallenge with 10,000 viable 9LGS cells. Moreover a single sc immunization with 5,000,000 untreated 9LGS cells prior to ic rec hallenge boosted survival from 30% to 100%. The relevance of these observat ions to strategies of preclinical experimentation for immunoprophylaxis of malignant gliomas is discussed.