A rat model for brain tumor immunotherapy is described that closely mimics the type of treatment that could be administered to humans. It involves surgical implantation of a permanent cannula in the brain, through which tumor cells and various effector cells and/or cytokines can be injected. The advantage of this system over more conventional animal surgical procedures is that conscious animals can be treated multiple times while avoiding morbidity and mortality associated with reoperative procedures. Using this system to study adoptive immunotherapy for brain tumors, we provide evidence that the 9L gliosarcoma tumor from the Fischer rat strain can be reduced or destroyed in situ following adoptive immunotherapy with specifically activated cytotoxic T lymphocytes.
We report the development of cytotoxic T lymphocytes specific for an allogeneic brain tumor in a rat model. DA strain cytotoxic T cell precursors stimulated by an allogeneic tumor (9L gliosarcoma) from the Fischer rat could generate a population of cytotoxic T lymphocytes that lysed the allogeneic 9L tumor but failed to lyse other targets, including Fischer concanavalin-A(ConA)-stimulated lymphoid blast targets. DA T cells depleted of reactivity to the Fischer haplotype (DA-F) retained reactivity to the 9L tumor, demonstrating that T cell precursors with specificity for normal Fischer alloantigens were not required for the generation of a response to the 9L Fischer tumor. The preferential lysis of the tumor target did not simply reflect a higher density of Fischer target antigens on the tumor than that found on normal Fischer ConA blast targets. First, the relative densities of class I antigen on the 9L tumor and normal Fischer ConA blasts were comparable. Second, cytotoxic T cells could not be generated from DA-F precursors when Fischer ConA blasts were used as stimulators. If DA-F T cells were simply responding to the higher density of Fischer antigen found on 9L tumor, it would have been expected that the ConA blasts expressing comparable levels of antigen to that found on the tumor would have generated cytotoxicity for both the 9L and ConA targets. We conclude that the cytotoxic T cells are specific for a determinant expressed only by the tumor. Such tumor-specific cytotoxic T cells could be useful in vivo for adoptive immunotherapy of brain tumors.
Various studies have provided evidence that peripheral T-cells from the diabetes-prone BB-DP rat are abnormal in function and cell surface phenotype. These characteristics have often been interpreted as indicators of immaturity and/or short life span. In this study, we describe a CD4-dependent signaling abnormality in BB-DP peripheral T-cells. In spite of the fact that CD4 plays a critical role in thymocyte development, the abnormal signaling does not appear to influence thymocyte development at the stage when the T-cell receptor is rearranged and the recombinase enzymes RAG-1 and RAG-2 transcripts are downregulated. Therefore, if a maturation defect leading to the seeding of the periphery with immature T-cells occurs in the BB-DP rat, it does not preclude the initial selection of the self major histocompatibility complex-restricted T-cell repertoire.
Gliosarcomas are an aggressive brain cancer that can become metastatic. Previously, we used a monoclonal antibody, designated H5, to isolate a tumor-associated antigen (TAA) expressed by 9L, a gliosarcoma line isolated from Fischer 344 (F344) rats. This TAA was tentatively identified as vimentin via mass spectrometry. In this project, we compared the level of vimentin mRNA in 9L cells to that of three types of glial cells: microglial cells, astrocytes, and oligodendrocytes isolated from F344 rats via qPCR. The level of vimentin mRNA in 9L cells was significantly upregulated as compared to the expression levels in all three types of glial cells. Similar research on carcinomas has identified vimentin as being involved in metastatic tumors and is now used as a genetic marker of this specific type of cancer. This research suggests that vimentin mRNA in 9L undergoes similar upregulation to that of carcinomas.
Cell surface antigens play a distinct role in the process of cell transformation and proliferation. The malignant, transformed counterparts of glial cells are referred to as glioma cells. Tumors or cancers resulting from the proliferation of these glioma cells constitute some of the most lethal types of cancer. We have characterized a tumor-associated antigen (TAA) expressed on the cell membrane of the 9L rat glisoarcoma (9L-Ag). Previous work has identified this antigen as a glycoprotein. In this study, we further characterize expression of 9L-Ag by normal brain cells, 9L cells, and a non-glial tumor cell line (P3X3Ag8.653). Characterization of 9L-Ag may provide a better understanding of the transformation processes from a normal to a malignant cell, and the role that 9L-Ag and similar TAAs may play in these processes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.