免疫学技术

Immunotoxins, characterized by tumor-specific cytotoxicity and high potency, have been developed as one of the new promising treatment modalities for primary malignant brain tumors (1–3). Fusion toxins bind to the cell-surface receptor specific for them, are internalized by recep ...

The major dose-limiting toxicity associated with ricin-conjugated immunotoxins (ITs) is vascular leak syndrome (VLS). IT-induced VLS appears to be dose dependent, occurs 2–4 d posttreatment (1–6), and is thought to be a result of the toxin moiety, rather than the targeting moiety, because VLS ...

Interleukin-4 (IL-4) is a pleiotropic immune regulatory cytokine that has been extensively studied in the last decade. Activated T-lymphocytes, mast cells, and basophils (1–3) produce it. Consistent with the pleiotropic nature of this molecule, the receptors for IL-4 have been identifi ...

Current treatment for malignant gliomas, which includes surgery, radiation therapy, and chemotherapy, is associated with a poor prognosis (1, 2). Patients with glioblastoma multiforme have an estimated 2 yr survival of less than 20% (1). Leptomeningeal carcinomatosis carries an esti ...

Monoclonal antibodies (MAbs) recognizing tumor-associated antigens (TAA) have been widely used to selectively deliver toxic compounds to neoplastic cells. In most studies, tumor targeting was achieved by the use of immunotoxins (IT) generated by chemical conjugation of an antibo ...

The role of protein tyrosine kinases (PTKs) in the survival of cancer cells and their potential use in anticancer therapy has led to their selection as anticancer drug targets. Tyrosine kinases which are being studied for this purpose include epidermal growth factor receptor (EGFR) (1–6), Jan ...

Tumor growth beyond a size of 1-2 mm3 requires new blood supply to sustain the nutritional and oxygen demands of the proliferating cancer cells (1). Tumor neovascularization is a complex process involving endothelial cell proliferation, matrix degradation, endothelial cell migrat ...

The purpose of this chapter is to describe the method of treating lymphokine-activated killer (LAK) cells with retroviral immunotoxins (retIT) so that these cells can express and secrete immunotoxins (IT). The intent is to use LAK as a vehicle to deliver IT therapy directly to leukemia cells in vi ...

Immunotoxins provide the opportunity to make neurotoxic lesions of specific neurochemically-defined neuronal populations (see Chapter 17) by targeting cell-surface antigens that are uniquely expressed by the cells of interest. The greatest application of these toxins in the s ...

This chapter describes the use of antineuronal immunotoxins to make selective neural lesions. The immunotoxin approach (immunolesioning) has significantly advanced the art of making neural lesions, combining the selectivity of monoclonal immunotoxins with various behav ...

The past several years have seen great optimism resulting from the deployment of highly active antiretroviral therapies for the treatment of HIV infection. Combinations of reverse transcriptase and protease inhibitors can induce suppression of viremia, reversal of immunodefi ...

Crosslinking reagents are valuable tools used to determine the quarternary and subunit structures of proteins (1,2). Other applications for crosslinkers include the determination of protein-protein interactions, analysis of proteins in cellular membranes, and the identif ...

Class I human leukocyte antigen (HLA-I) alleles have been described as themost polymorphic human antigens (1-4). To date, there are more than 500 HLA- I alleles which have been officially assigned by the World Health Organization Nomenclature Committee for Factors of the HLA System (5). This num ...

Major histocompatibility complex class I (MHC-I) molecules are highly polymorphic cell surface expressed molecules that bind antigenic (Ag) peptides in the endoplasmic reticulum (ER) and transport them to the cell surface for presentation to cytotoxic T-cells (1). The MHC-I complex is ...

Major histocompatibility complex class I (MHC-I) molecules alert cytotoxic T-lymphocytes to the presence of intracellular pathogens and tumors by presenting short peptides derived from pathogen- or tumor-specific proteins. To present a peptide, an MHC-I heavy chain (HC) binds the p ...

Immunization of mice, with preparations of heat shock proteins (HSPs) isolated from tumors or virus-infected cells, has been shown to elicit specific protective immunity against the tumor or the virus-infected cells used as the source of the HSP. This phenomenon has been shown to be general, in t ...

Peptides that bind major histocompatibility complex (MHC) products exhibit allele-specific sequence motifs. The motifs, however, are neither necessary nor sufficient for binding. In particular, about 66% of the peptides that exhibit motifs do not bind the corresponding MHC molecu ...

T lymphocytes interact with protein antigens (Ags) in the form of peptides bound to self-major histocompatibility complex (MHC) molecules displayed at the surface of antigen-presenting cells (APC) (1, 2). Dissection of the different T-cell receptor (TCR)-mediated functions elici ...

Many of the important properties of T-cells are not imprinted by the genetic program of the cell. Clonotypic expression of receptors, major histocompat- ibility complex (MHC) restriction, and self tolerance are all properties that are determined somatically during the development of an ...

Differentiated CD4+T-cells produce a restricted set of cytokines, allowing their subdivision into two discrete populations: T-helper 1 (Th1), characterized by secretion of interleukin 2 (IL-2) and interferon γ (IFN-γ); and Th2, selectively producing IL-4, IL-5, and IL-10 (1). Polarized s ...