S Zaremba's research while affiliated with National Institutes of Health and other places

Publications (24)

Article
The identification of an agonist peptide (YLSGADLNL, designated CAP1-6D) to an immunodominant cytotoxic T-lymphocyte (CTL) epitope (designated CAP1) of human carcinoembryonic antigen (CEA) has previously been reported. The agonist peptide harbors a single amino acid substitution at a non-MHC anchor residue and is proposed to exert its effects at th...
Article
A new era involving the evaluation of recombinant vaccines for colon cancer has begun with the concurrent emergence of insights and technologies in the fields of molecular biology and immunology. These advances include (I) the identification and cloning of an array of genes associated with the neoplastic process, such as oncogenes, suppressor genes...
Article
Full-text available
Prostate-specific Ag (PSA), which is expressed in a majority of prostate cancers, is a potential target for specific immunotherapy. Previous studies have shown that two 10-mer PSA peptides (designated PSA-1 and PSA-3) selected to conform to human HLA class I-A2 motifs can elicit CTL responses in vitro. A longer PSA peptide (30-mer) designated PSA-O...
Article
A new era involving the evaluation of recombinant cancer vaccines has begun with the concurrent emergence of insights and technologies in the fields of molecular biology and immunology. These advances include: The identification and cloning of an array of genes associated with the neoplastic process, such as oncogenes, suppressor genes, genes encod...
Article
Prostate-specific Ag (PSA), which is expressed in a majority of prostate cancers, is a potential target for specific immunotherapy. Previous studies have shown that two 10-mer PSA peptides (designated PSA-1 and PSA-3) selected to conform to human HLA class I-A2 motifs can elicit CTL responses in vitro. A longer PSA peptide (30-mer) designated PSA-O...
Article
Full-text available
CTL lines have now been generated against defined peptides of a range of human tumor-associated antigens (TAAs). One of the potential uses of these epitope-specific CTLs is in adoptive transfer immunotherapy. This is a modality, however, that will require long-term in vitro culture of CTLs. To date, little has been reported concerning the phenotypi...
Article
A vaccination strategy designed to enhance the immunogenicity of self-antigens that are overexpressed in tumor cells is to identify and slightly modify immunodominant epitopes that elicit T-cell responses. The resultant T cells, however, must maintain their ability to recognize the native configuration of the peptide-MHC interaction on the tumor ce...
Article
Full-text available
Protein antigens are presented to cytotoxic T lymphocytes as small peptides (approximately 9-10 amino acids long) bound to class I molecules of the major histocompatibility complex. The identification of tumor-associated antigens and specific peptide epitopes (i.e., antigenic determinants) may be useful in the development of anticancer vaccines. Th...
Article
Mutant ras p21 proteins contain sequences which distinguish them from normal endogenous ras and, thus, may represent unique epitopes for T cell recognition of antigen bearing tumor cells. Here, we examined the capacity of a mutant K-ras 9-mer peptide to induce in vivo CD8+ cytotoxic T lymphocytes (CTL). The peptide chosen reflected positions 4-12 o...
Article
Alterations in the ras p21 protein have been associated with both rodent and human neoplasia. Thus, mutated ras p21 proteins may bear unique antigenic epitopes for immune recognition, such as by T cells, which have been implicated in host antitumor activity. Synthetic peptides that mimic segments of mutated ras p21 have been reported to be immunoge...
Article
The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates. Our...
Article
Chimeric antibodies have been produced against a pancarcinomic tumor associated antigen, TAG-72, by fusing the genes for the variable region of mouse MAb B72.3 to the genes for the constant region of human IgG. In our efforts to optimize the pharmacokinetics of plasma clearance and the efficiency of tumor localization and penetrance of cB72.3, we h...
Article
Monoclonal antibody (MAb) B72.3 reacts with TAG-72, a high-molecular-weight mucin expressed on several types of human carcinoma, and is currently being used in clinical trials for the diagnosis and therapy of human carcinoma. An expression construct containing cDNA encoding an immunoglobulin (Ig) heavy chain, with the variable region of murine MAb...
Article
Monoclonal antibody (MAb) B72.3 reacts with TAG-72, a high-molecular-weight mucin expressed on several types of human carcinoma, and is currently being used in clinical trials for the diagnosis and therapy of human carcinoma. An expression construct containing cDNA encoding an immunoglobulin (Ig) heavy chain, with the variable region of murine MAb...
Article
Full-text available
Cat-301 and VC1.1 are monoclonal antibodies that recognize surface-associated molecules on subsets of mammalian CNS neurons. Earlier work demonstrated that Cat-301 recognizes a 680-kDa chondroitin sulfate proteoglycan (PG). VC1.1 has been shown to recognize 3 polypeptide bands on Western blot analysis; a major band at 95-105 kDa and additional band...
Article
Full-text available
Monoclonal antibody Cat-301 recognizes a surface-associated proteoglycan on subsets of neurons in the mammalian CNS (Hockfield and McKay, 1983). The expression of Cat-301 immunoreactivity on Y cells in the cat LGN is sharply reduced by early visual deprivation (Sur et al., 1988). We employed an immunosuppression strategy (Hockfield, 1987) to furthe...
Article
Full-text available
Cat-301 and VC1.1 are monoclonal antibodies that recognize surface- associated molecules on subsets of mammalian CNS neurons. Earlier work demonstrated that Cat-301 recognizes a 680-kDa chondroitin sulfate proteoglycan (PG). VC1.1 has been shown to recognize 3 polypeptide bands on Western blot analysis; a major band at 95-105 kDa and additional ban...
Article
Monoclonal antibody Cat-301 recognizes a cell-surface proteoglycan on subsets of neurons in several areas of the cat and macaque monkey central nervous system. In striate and extrastriate visual cortex of the macaque, the distribution of Cat-301-positive neurons demonstrates features of cellular organization that correlate with previously described...
Article
Monoclonal antibody Rat 401 recognizes subsets of cells in the developing central and peripheral nervous systems. Previous studies have shown that in the central nervous system (CNS) Rat 401 immunoreactivity diminishes sharply with cellular differentiation. Here we have examined the time course, cellular localization, and biochemical nature of the...
Article
Excerpt The neurons in the mature mammalian central nervous system (CNS) are an enormously diverse group of cells. The acquisition of mature, differentiated neuronal properties takes place over an extended developmental period, through a number of different mechanisms. Some of the very last events in neuronal development occur late in the postnatal...
Article
Monoclonal antibody Cat-301 was previously shown to recognize a surface-associated antigen on subsets of mammalian CNS neurons whose expression is regulated by neuronal activity early in an animal's postnatal life. We now present the partial purification and characterization of the Cat-301 antigen and demonstrate that it is a chondroitin sulfate pr...

Citations

... Studies have identified PSA-derived peptides that activate tumor-reactive CD8+ cytotoxic T lymphocytes (CTLs) when presented by human leukocyte antigen-A2 (HLA-A2) and HLA-A3 [75][76][77] . Simultaneous induction of tumor-reactive CTLs and HLA-A2/A3-restricted epitopes of PSA has been achieved using specific oligopeptides [78][79][80] . Additionally, HLA-A24-restricted PSA peptides elicited peptide-specific CTLs in PCa patients and HLA-A*2402restricted CTLs in transgenic mice [81][82][83] . ...
... In many brain regions, PNNs preferentially enwrap inhibitory parvalbumin-positive neurons, which are highly active and involved in critical periods of brain development, and play a crucial role in the regulation of neuronal functions and synaptic plasticity (Cabungcal et al., 2013;Fawcett et al., 2019;Reichelt et al., 2019). In the cerebellar cortex, Lugaro/globular cells, which receive strong GABAergic inhibition from PCs via their axon collaterals, are recognized by a monoclonal antibody against aggrecan, Cat-301 (Sahin and Hockfield, 1990;Zaremba et al., 1990;Crook et al., 2007), which means that they are surrounded by PNNs. On the other hand, both the cell bodies and the proximal dendrites of large and excitatory DCN neurons, which are primarily glutamatergic (Telgkamp and Raman, 2002;Uusisaari et al., 2007), are surrounded by PNNs (Figures 1C, 3A) in which aggrecan is the primary CSPG (Zaremba et al., 1990;Carulli et al., 2004Carulli et al., , 2006Carulli et al., , 2007Zimmermann and Dours-Zimmermann, 2008;Foscarin et al., 2011;Bekku et al., 2012). ...
... We have investigated the ability of an oligopeptide, PSA-OP, to induce cytotoxic T cell immune responses against PSA. PSA-OP is a 30-mer peptide containing three HLA-A2-binding epitopes (27), as well as an epitope for HLA-A3 (44) and, potentially, HLA-A11 (that shares a common anchor motif of V at position 2 and K at position 9) (45). In these studies, we have generated two HLA-A2-restricted cytotoxic T cell lines (T1-PSA-OP and T2-PSA-OP) and two HLA-A3-restricted cytotoxic T cell lines (T3-PSA-OP and T4-PSA-OP) from two HLA-A2 donors and two HLA-A3 donors, respectively. ...
... In an attempt to overcome the shortcomings of murine and intact IgG and to profit from the excellent specific reactivity of CC49, Slavin-Chiorini bioengineered a CDRgrafted humanized monoclonal antibody with a C H 2 domain deletion (ΔCH2) [98]. Deletion of the C H 2 domain of IgG had already been reported to result in faster tumour uptake and more rapid blood clearance [99][100][101]. The recombinant IgG molecule HuCC49ΔCH2 combined, for the first time, a fast blood clearance with the reduced potential for eliciting a HAMA response. As anticipated, radioiodinated ( 125/131 I) HuCC49ΔCH2 constructs demonstrated faster blood clearance in both athymic and SCID mice bearing human colon carcinoma xenografts and effective localization to tumour xenographs while showing minimal deposition in healthy tissues [98,101,102]. ...
... Developmental formation of PNNs is activity-dependent, and several brain regions including barrel cortex, thalamus, visual cortex, and vocal center in songbirds show underdeveloped PNNs if deprived of activity, suggesting a high malleability of PNNs (Guimarães et al., 1990;Lander et al., 1997;Pizzorusso et al., 2002;McRae et al., 2007;Nakamura et al., 2009). Although PNNs in the mature CNS appear to be largely stable in a normal physiological state, emerging evidence suggests bidirectional changes in the structure and numerical density of PNNs on a cyclic basis as well as under specific conditions such as drug addiction, maternal hormone fluctuations, and chronic pain (Lasek et al., 2018;Pantazopoulos et al., 2020;Uriarte et al., 2020;Harkness et al., 2021;Mascio et al., 2022). ...
... The ECM also has an important role in regulating synaptic function and development [37]. As the brain develops postnatally, the composition of the ECM changes to facilitate this function [38,39]. In the early stages of development, the ECM is dynamic and permis-Int. ...
... In macaques, stripes of the same type have a center-to-center distance of around 4.0 mm and a width ranging from 0.7 to 1.3 mm (Shipp and Zeki, 1985;Tootell and Hamilton, 1989). In humans, these widths are approximately doubled in size (Hockfield et al., 1990;Tootell and Taylor, 1995;Adams et al., 2007). ...
... Neural cell-adhesion molecule (N-CAM, Zaremba et al. 1990 ) and neuron-specific class III βtubulin isotype (Dráberová et al. 1998), both being the markers of neural cells, and endoderm-specific cytokeratin Endo-A (Kanungo et al. 2000) were quantified by Western blot analysis. For Western blot analysis, both cultured EC cells and mouse fetal brain tissue (developing neopallium) were processed according to same protocol. ...
... Theyspeculated that the structure might be involved in insulating neurons (28). Later studies described PNN composition and the development of new antibodies for Chondroitin sulfate proteoglycans (CSPGs) (29,30), which were used to investigate individual CSPGs, particularly in the context of glial scar formation (31). The use of ChABC to disrupt PNN structure by degrading GAGs and thus removing the PNN that has been deposited around neurons, resulted in memory loss and reopening of critical periods. ...
... IC a number of other proteoglycans have been shown to support synaptic function. Aggrecan has been shown to stabilize synaptic structure, while brevican and neurocan are important for the maintenance of inhibitory and excitatory synapses (Zaremba et al., 1989;Gottschling et al., 2019;Schmidt et al., 2020). The proteoglycan neurocan is also known for its roles in the development of PNs, while phosphacan is better understood in the aging brain (Nishiwaki et al., 1998;Gottschling et al., 2019;Schmidt et al., 2020). ...