Intratumoral autologous mononuclear cells in the treatment of recurrent glioblastoma multiforme

Abstract

Four patients with malignant gliomas recurring after surgical resection, radiotherapy and chemotherapy were entered into a trial of immunotherapy. Partial removal of the recurrent tumors was performed and autologous mononuclear cell infusions were given into the resection cavity via a subgaleal reservoir that had been inserted at the time of tumor resection. Mononuclear cells were obtained using a cell separator and Ficoll-hypaque separation techniques. Patients were followed carefully with clinical examinations, CT brain scans and immunological testing. All patients have died and complete autopsies were done. We looked specifically for evidence of mononuclear cell penetration into the tumor and possible adverse effects on the normal brain or in the rest of the body. The results indicate that this type of therapy can be performed safely and may be useful in the treatment of patients with malignant gliomas.

Genetics and immunotherapy: using the genetic landscape of gliomas to inform management strategies

“…Early studies utilized peripheral blood mononuclear cells (PBMCs), lymphokineactivated killer cells, consisting of IL-2-activated PBMCs, and tumor-infiltrating lymphocytes (TILs), and administered cells into the tumor cavity after resection. Most patients did not experience any adverse events, but there was also no significant impact on outcomes [59][60][61]. One novel cell-based strategy that has been successful is the transduction of T-cells with T-cell receptor signaling molecules and chimeric antigen receptors (CARs) that recognize TSAs.…”

Cellular Immunotherapy for Malignant Brain Tumors

“…In the past decade, different cell types have been studied to best induce antitumor immunity in tumor bearing hosts. Different cell types that have been used include (i) peripheral blood mononuclear cells (PBMCs) or peripheral blood lymphocytes (PBL) [148,149], (ii) lymphokine-activated killer cells (LAKS) [150][151][152], (iii) mitogen-activated killer cells (MAKs) [153,154], (iv) tumor infiltrating lymphocytes (TILs) [155], and (v) antigen specific cytotoxic lymphocytes [156,157]. In 1992, Riddell et al [158] reported that the adoptive transfer of T cell clones restored viral immunity in patients undergoing hematopoietic stem cell transplant.…”

“…Adoptive cell transfer was first studied in hematopoietic stem cell transplant in a non-myeloablative setting used for the treatment of chronic myeloid leukemia [160] and was further developed for solid tumors. In 1984, Steinbok et al [148] was the first to demonstrate the safety and feasibility if adoptive immunotherapy for brain malignancies, but saw no measurable benefit to patient outcome. This landmark study was based on previous observations that GBM patients had observed lymphocytic infiltrates at tumor sites [148], suggesting that there was an attempt to mount an immune response by endogenous immune cells [161,162].…”

“…In 1984, Steinbok et al [148] was the first to demonstrate the safety and feasibility if adoptive immunotherapy for brain malignancies, but saw no measurable benefit to patient outcome. This landmark study was based on previous observations that GBM patients had observed lymphocytic infiltrates at tumor sites [148], suggesting that there was an attempt to mount an immune response by endogenous immune cells [161,162]. The logic follows that perhaps other systemic factors were preventing these lymphocyte infiltrates from properly reaching the tumor site, or preventing lymphocyte activation.…”

“…The logic follows that perhaps other systemic factors were preventing these lymphocyte infiltrates from properly reaching the tumor site, or preventing lymphocyte activation. To circumvent this and the known immune deficits of glioma patients, Steinbok and colleagues [148] collected PBMCs from patients and re-infused the cells into their post-surgical cavities. Though no beneficial clinical outcomes were observed, this study established the feasibility and beginnings of adoptive immunotherapy in CNS malignancies.…”