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PubMed1995

Correction of the growth defect in dwarf mice with nonautologous microencapsulated myoblasts--an alternate approach to somatic gene therapy.

Most of the currently approved human gene therapy protocols depend on genetic modification of autologous cells. We propose an alternate and potentially more cost-effective approach by implanting genetically modified "universal" cell lines to deliver desired gene products to nonautologous recipients. The recombinant allogeneic cells are protected from rejection after implantation by enclosure within immuno-protective alginate-poly-L-lysine-alginate microcapsules. The clinical efficacy of this strategy is now demonstrated by implanting microencapsulated allogeneic myoblasts engineered to secrete mouse growth hormone into the growth hormone-deficient Snell dwarf mice. The treated mutants attained increases in linear growth, body weights, peripheral organ weights, and tibial growth plate thickness significantly greater than those of the untreated controls. Secondary response to the exogenous growth hormone stimulation also resulted in increased fatty acid metabolism during the first month post-implantation. The microcapsules retrieved after about 6 months of implantation appeared intact. The encapsulated myoblasts retained a viability of > 60% and continued to secrete mouse growth hormone. Thus, implantation of nonautologous recombinant cells corrected partially the pleiomorphic effects of a transcription factor mutation in the Snell dwarf mice and the encapsulated cells remained functional for at least 6 months. This simple method of delivery recombinant gene products in vivo is a benign procedure, obviates the need for patient-specific genetic modification, and is amenable to industrial-scale quality control. It should have wide applications in therapies requiring a systemic continuous supply of recombinant gene products.

Alginates↗
PubMed2025

Genetic Landscape of Opsoclonus-Myoclonus-Ataxia Syndrome in Children.

BACKGROUND: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neurological disorder, with involuntary rapid saccadic conjugate eye movements as one of characteristics, primarily affecting the cerebellum. While the exact pathogenesis remains unclear, genetic and autoimmune factors have been suggested to contribute to its development. METHODS: We enrolled patients diagnosed with OMAS before the age of 18 years at a pediatric neuroimmunology clinic in Boston, United States, using the 2004 Genoa Criteria. Whole genome sequencing was conducted for the patients and their biological parents in all cases, with one case including an unaffected twin sibling. RESULTS: De novo germline variants (DNVs) in probands were identified and validated and analyses of structural variants, recessive variants in neuroimmune-associated genes, and high-resolution human leukocyte antigen (HLA) typing were performed. Our study included 42 patients, 23 of whom had neuroblastoma. We found 12 confirmed DNVs in protein-coding regions in nine patients (29.0% of 31 from 30 trios and 1 quartet). Ten patients (23.8% of 42) had rare homozygous or compound heterozygous variants known to alter protein function, affecting 11 genes. Notably, the major histocompatibility complex, class II, DR beta 1 (HLA-DRB1) &#x2217;01 allele was observed in 27 out of 84 (32.1%) alleles in the patients, significantly higher than that in the general population (chi-square test, P < 0.0001). In one case, a potential genetic modifier of OMAS with severe cerebellar atrophy was identified, associated with a protein-truncating DNV in the CACNA2D2 gene. CONCLUSIONS: This first genome sequencing study reveals potential genetic contributors to OMAS, implicating polygenic predisposition-with HLA-DRB1&#x2217;01 as a possible factor-combined with nongenetic risk factors like neuroblastoma.

Humans↗
PubMed2001

Interferon-gamma modulates prolactin and tissue factor expression in differentiating human endometrial stromal cells.

Cytokines such as interferon-gamma (IFNgamma) released by resident uterine immune cells are thought to influence the expression of differentiated function in the human endometrium. Decidualization of the stromal cell compartment is confined to the superficial endometrial layer in the nonpregnant uterus. To explore the molecular mechanism underlying the spatial expression of the decidual phenotype, the effect of IFNgamma on the induction of two well characterized markers of endometrial stromal (ES) cell differentiation, PRL and tissue factor (TF), has been investigated. IFNgamma antagonizes cAMP-mediated PRL protein and messenger RNA expression in primary ES cell cultures through inhibition of decidual PRL promoter activity. In parallel, IFNgamma stimulates Stat-1 (signal transducer and activator of transcription-1) expression, phosphorylation, and translocation to the nucleus. Exogenously expressed Stat-1 potently represses decidual PRL promoter activation, indicating the potential for the inhibitory effects of IFNgamma to be mediated by Stat-1. We demonstrate that although the coactivator CREB-binding protein/p300 is essential for decidual PRL transcription, this coactivator does not appear to be the target for IFNgamma-mediated repression. By contrast, IFNgamma has little effect on cAMP-mediated TF expression, but induces TF in ES cells not exposed to a decidualizing stimulus. This suggested that in vivo TF expression may not be restricted to decidualizing cells of the superficial layer and was confirmed by immunohistochemical analysis demonstrating intense TF staining in the basal stromal compartment during the regeneration phase of the cycle. The differential sensitivity of decidualization-associated genes to IFNgamma illustrates its potential role as a selective biological response modifier that influences regional function within the endometrium.

Cell Differentiation↗
PubMed2001

Heritability of hippocampal size in elderly twin men: equivalent influence from genes and environment.

Recent studies have established that environmental factors can modify hippocampal structure and enhance function in adult rodents, but the extent to which genes and the environment exert differential contributions to hippocampal structural integrity in humans is unknown. Here, we applied the twin model in a large sample of elderly twin men to examine in late life the balance of environmental and genetic effects on the size of the hippocampus in comparison with other brain structures. This study provides novel evidence that the volume of the hippocampus, as measured on MRI, is subject to substantially less genetic control than are comparison brain regions also measured: temporal horn volume, midsagittal area of the corpus callosum, and intracranial volume (ICV). In particular, about 60% of the temporal horn variance and 80% of the callosal and ICV variance was attributable to genetic influences, whereas only 40% of the hippocampal variance was attributable to genetic influences. These results suggest that environment, whether by itself or in interaction with genes, has the potential of exerting greater and possibly longer control in modifying hippocampal size than other brain regions that are under greater genetic control. Considering the potential of environmental modification of this structure suggested by lower heritability, the hippocampus appears well-suited to support the dynamic processes of encoding and consolidation of new, declarataive memories.

Aged↗
PubMed2002

Drought and oxidative load in the leaves of C3 plants: a predominant role for photorespiration?

Although active oxygen species are produced at high rates in both the chloroplasts and peroxisomes of the leaves of C3 plants, most attention has focused on the potentially damaging consequences of enhanced chloroplastic production in stress conditions such as drought. This article attempts to provide quantitative estimates of the relative contributions of the chloroplast electron transport chain and the glycolate oxidase reaction to the oxidative load placed on the photosynthetic leaf cell. Rates of photorespiratory H2O2 production were obtained from photosynthetic and photorespiratory flux rates, derived from steady-state leaf gas exchange measurements at varying irradiance and ambient CO2. Assuming a 10% allocation of photosynthetic electron flow to the Mehler reaction, photorespiratory H2O2 production would account for about 70% of total H2O2 formed at all irradiances measured. When chloroplastic CO2 concentration rates are decreased, photorespiration becomes even more predominant in H2O2 generation. At the increased flux through photorespiration observed at lower ambient CO2, the Mehler reaction would have to account for more than 35% of the total photosynthetic electron flow in order to match the rate of peroxisomal H2O2 production. The potential signalling role of H2O2 produced in the peroxisomes is emphasized, and it is demonstrated that photorespiratory H2O2 can perturb the redox states of leaf antioxidant pools. We discuss the interactions between oxidants, antioxidants and redox changes leading to modified gene expression, particularly in relation to drought, and call attention to the potential significance of photorespiratory H2O2 in signalling and acclimation.

Acclimatization↗
PubMed2003

The interaction between the fiber knob domain and the cellular attachment receptor determines the intracellular trafficking route of adenoviruses.

Most of the presently used adenovirus (Ad) vectors are based on serotype 5. However, the application of these vectors is limited by the native tropism of Ad5. To address this problem, a series of fiber chimeric vectors were produced to take advantage of the different cellular receptors used by Ad of different subgroups. In this study we utilize an Ad5-based chimeric vector containing sequences encoding the Ad35 fiber knob domain instead of the Ad5 knob (Ad5/35L) to analyze factors responsible for selection of intracellular trafficking routes by Ads. By competition analysis with recombinant Ad5 and Ad35 knobs we showed that the Ad5/35L vector infected cells through a receptor different from the Ad5 receptor. Intracellular trafficking of Ad5 and Ad5/35L viruses was analyzed in HeLa cells by tracking fluorophore-conjugated Ad particles, by immunostaining for capsid hexon protein, by electron microscopy, and by Southern blotting for viral DNA. These studies showed that the interaction with the Ad35 receptor(s) predestines Ad5/35L vector to intracellular trafficking pathways different from those of Ad5. Ad5 efficiently escaped from the endosomes early after infection. In contrast, Ad5/35L remained longer in late endosomal/lysosomal compartments and used them to achieve localization to the nucleus. However, a significant portion of Ad5/35L particles appeared to be recycled back to the cell surface. This phenomenon resulted in significantly less efficient Ad5/35L-mediated gene transfer compared to that of Ad5. We also demonstrated that the selection of intracellular trafficking routes was determined by the fiber knob domain and did not depend on the length of the fiber shaft. This study contributes to a better understanding of the mechanisms that govern the infection of retargeted, capsid-modified vectors which have potential application for hematopoietic stem cell and tumor gene therapy.

Adenoviruses, Human↗
PubMed2005

Id1 gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis.

BACKGROUND: Transplantation of endothelial progenitor cells has been proposed as a potential strategy for therapeutic revascularization. However, the limited endogenous cell pool and the related technical difficulties constitute clinically important disadvantages to autologous transplantation. In this study we investigated whether fully differentiated endothelial cells (ECs) modified with gene transfer of Id1, a helix-loop-helix transcription factor involved in angiogenesis, have the potential to contribute to therapeutic angiogenesis. METHODS AND RESULTS: The Id1 gene was transferred into human umbilical vein ECs (HUVECs) via a Sendai virus vector. Id1 stimulated migration, proliferation, and capillary-like tube/cord formation of HUVECs. In addition, Id1 reduced serum deprivation-induced HUVEC apoptosis, as shown by FACS analysis with annexin V and TUNEL staining. Transplantation of Id1-overexpressing HUVECs accelerated recovery of blood flow as evaluated by laser-Doppler perfusion imaging, increased capillary density, and improved the rate of limb salvage compared with the transplantation of control HUVECs. Histochemical analysis revealed that the regenerated vascular networks of limbs transplanted with Id1-overexpressing HUVECs contained numerous HUVECs, some of which were in a proliferative state. Untransfected HUVECs were also incorporated with Id1-transfected HUVECs, suggesting the noncell autonomous effect of Id1. Finally, angiopoietin-1 was upregulated in Id1-overexpressing HUVECs and functionally contributed to the in vitro angiogenic effect of Id1. CONCLUSIONS: Id1 gene transfer conferred HUVECs with an angiogenic property, contributing to neovascularization after transplantation into ischemic lesions. Transplantation of Id1-overexpressing mature ECs may serve as a novel and useful strategy for therapeutic angiogenesis.

3' Untranslated Regions↗
PubMed2006

Modified signal-to-noise: a new simple and practical gene filtering approach based on the concept of projective adaptive resonance theory (PART) filtering method.

UNLABELLED: Considering the recent advances in and the benefits of DNA microarray technologies, many gene filtering approaches have been employed for the diagnosis and prognosis of diseases. In our previous study, we developed a new filtering method, namely, the projective adaptive resonance theory (PART) filtering method. This method was effective in subclass discrimination. In the PART algorithm, the genes with a low variance in gene expression in either class, not both classes, were selected as important genes for modeling. Based on this concept, we developed novel simple filtering methods such as modified signal-to-noise (S2N') in the present study. The discrimination model constructed using these methods showed higher accuracy with higher reproducibility as compared with many conventional filtering methods, including the t-test, S2N, NSC and SAM. The reproducibility of prediction was evaluated based on the correlation between the sets of U-test p-values on randomly divided datasets. With respect to leukemia, lymphoma and breast cancer, the correlation was high; a difference of >0.13 was obtained by the constructed model by using <50 genes selected by S2N'. Improvement was higher in the smaller genes and such higher correlation was observed when t-test, NSC and SAM were used. These results suggest that these modified methods, such as S2N', have high potential to function as new methods for marker gene selection in cancer diagnosis using DNA microarray data. AVAILABILITY: Software is available upon request.

Algorithms↗
PubMed2003

Validation of GABA(A) receptor subtypes as potential drug targets by using genetically modified mice.

A key issue for drug discovery in the post genomic era is target validation. This is particularly important when considering the CNS, where currently the majority of drug targets are neurotransmitter receptors that are known to exist as multi-gene families. The GABAergic system, which is the major inhibitory neurotransmitter system in the CNS, is no exception in that respect. The GABA(A) receptors, which are the site of action of a number of clinically used drugs such as benzodiazepines and barbiturates, exist in a large gene family. Existing drugs mediating their effects through the GABA(A) receptor are generally non-selective, i.e. will act at several subtypes of that receptor family. Thus, if we are both to refine existing therapeutic approaches, and develop novel approaches, a key question is to define which subtype(s) of the GABA(A) receptor family we should target; which will mediate the beneficial effects of a drug, and which could be responsible for unwanted side effects? One of the tools, which has been developed over the last decade to elucidate the function of a given gene, is the generation and analysis of gene-targeted mice. This review will summarize progress on identifying individual GABA(A) receptor subtypes as potential drug targets by using genetically modified mice.

Anesthetics↗
PubMed1995

Heterochromatin and gene expression in Drosophila.

Heterochromatin is both necessary for the expression of heterochromatic genes and inhibitory for the expression of euchromatic genes. These two properties of heterochromatin have been elucidated from the study of chromosome rearrangements that induce position effect variegation (PEV) in Drosophila melanogaster. Novel euchromatin-heterochromatin junctions can affect the expression of euchromatic and heterochromatic genes located several megabases away, distinguishing higher order chromatin structure from most other regulatory mechanisms. Studies of PEV promise insights into the basis for heterochromatin formation and the role of higher order chromatin and chromosome structure in gene regulation. We evaluate the models and experimental data that address the mechanisms of PEV in different cell types, the potential functions of modifiers of PEV, and the relationship of PEV to other phenomena associated with variegated gene expression in Drosophila.

Animals↗
PubMed2006

Differential Delta expression underlies the diversity of sensory organ patterns among the legs of the Drosophila adult.

Many studies have shown that morphological diversity among homologous animal structures is generated by the homeotic (Hox) genes. However, the mechanisms through which Hox genes specify particular morphological features are not fully understood. We have addressed this issue by investigating how diverse sensory organ patterns are formed among the legs of the Drosophila melanogaster adult. The Drosophila adult has one pair of legs on each of its three thoracic segments (the T1-T3 segments). Although homologous, legs from different segments have distinct morphological features. Our focus is on the formation of diverse patterns of small mechanosensory bristles or microchaetae (mCs) among the legs. On T2 legs, the mCs are organized into a series of longitudinal rows (L-rows) precisely positioned along the leg circumference. The L-rows are observed on all three pairs of legs, but additional and novel pattern elements are found on T1 and T3 legs. For example, at specific positions on T1 and T3 legs, some mCs are organized into transverse rows (T-rows). Our studies indicate that the T-rows on T1 and T3 legs are established as a result of Hox gene modulation of the pathway for patterning the L-row mC bristles. Our findings suggest that the Hox genes, Sex combs reduced (Scr) and Ultrabithorax (Ubx), establish differential expression of the proneural gene achaete (ac) by modifying expression of the ac prepattern regulator, Delta (Dl), in T1 and T3 legs, respectively. This study identifies Dl as a potential link between Hox genes and the sensory organ patterning hierarchy, providing insight into the connection between Hox gene function and the formation of specific morphological features.

Animals↗
PubMed1999

Cooperative transcriptional activation by serum response factor and the high mobility group protein SSRP1.

Serum response factor (SRF) is a MADS box transcription factor that controls a wide range of genes involved in cell proliferation and differentiation. The MADS box mediates homodimerization and binding of SRF to the consensus sequence CC(A/T)6GG, known as a CArG box, which is found in the control regions of numerous serum-inducible and muscle-specific genes. Using a modified yeast one-hybrid screen to identify potential SRF cofactors, we found that SRF interacts with the high mobility group factor SSRP1 (structure-specific recognition protein). This interaction, which occurs in yeast and mammalian cells, is mediated through the MADS box of SRF and a basic region of SSRP1 encompassing amino acids 489-542, immediately adjacent to the high mobility group domain. SSRP1 does not bind the CArG box, but interaction of SSRP1 with SRF dramatically increases the DNA binding activity of SRF, resulting in synergistic transcriptional activation of native and artificial SRF-dependent promoters. These results reveal an important role for SSRP1 as a coregulator of SRF-dependent transcription in mammalian cells.

Amino Acid Sequence↗
PubMed1993

Delivery of recombinant gene products with microencapsulated cells in vivo.

If established cultured cell lines genetically modified to secrete desired gene products could be implanted in different allogeneic recipients without immune rejection, novel gene products would be delivered more cost effectively. We tested this strategy by encapsulating mouse Ltk- cells transfected with the human growth hormone (hGH) gene in immunoprotective perm-selective alginate microcapsules. Allogeneic mice implanted with these microcapsules demonstrated hGH in their circulation (0.1-1.5 ng/ml serum) within the first 2 weeks. Control mice implanted with only the transfected cells without microcapsules did not demonstrate significant levels of circulating hGH. By about 3 weeks, antibodies against hGH developed in the microcapsule-implanted mice. The immune response was detected only against the hGH and no other secretory products from the transfected cells. The antibody titer continued to escalate for more than three months, thus demonstrating indirectly the continued delivery of the growth hormone. The persistent expression of the transgene and survival of the transfected cells were verified when the microcapsules were retrieved periodically to demonstrate that the encapsulated cells remained viable, proliferative, and productive of hGH even by 78-111 days. In conclusion, delivering gene products with genetically modified allogeneic cells in vivo has been shown feasible for prolonged periods. This technology should have potential applications in somatic gene therapy and in treatment of other somatic diseases.

Animals↗
PubMed2006

Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS study.

BACKGROUND: Age at onset of Huntington's disease (HD) is correlated with the size of the abnormal CAG repeat expansion in the HD gene; however, several studies have indicated that other genetic factors also contribute to the variability in HD age at onset. To identify modifier genes, we recently reported a whole-genome scan in a sample of 629 affected sibling pairs from 295 pedigrees, in which six genomic regions provided suggestive evidence for quantitative trait loci (QTL), modifying age at onset in HD. METHODS: In order to test the replication of this finding, eighteen microsatellite markers, three from each of the six genomic regions, were genotyped in 102 newly recruited sibling pairs from 69 pedigrees, and data were analyzed, using a multipoint linkage variance component method, in the follow-up sample and the combined sample of 352 pedigrees with 753 sibling pairs. RESULTS: Suggestive evidence for linkage at 6q23-24 in the follow-up sample (LOD = 1.87, p = 0.002) increased to genome-wide significance for linkage in the combined sample (LOD = 4.05, p = 0.00001), while suggestive evidence for linkage was observed at 18q22, in both the follow-up sample (LOD = 0.79, p = 0.03) and the combined sample (LOD = 1.78, p = 0.002). Epistatic analysis indicated that there is no interaction between 6q23-24 and other loci. CONCLUSION: In this replication study, linkage for modifier of age at onset in HD was confirmed at 6q23-24. Evidence for linkage was also found at 18q22. The demonstration of statistically significant linkage to a potential modifier locus opens the path to location cloning of a gene capable of altering HD pathogenesis, which could provide a validated target for therapeutic development in the human patient.

Adolescent↗
PubMed2003

Strain-specific modification of lethality in fucose-deficient mice.

The FX locus encodes an essential enzyme in the de novo pathway of GDP-fucose biosynthesis. Mice homozygous for a targeted mutation of the FX gene manifest a host of pleiotropic abnormalities including a lethal phenotype that is almost completely penetrant in heterozygous intercrosses on a mixed genetic background. Here we have investigated genetic suppression of FX-mediated lethality. Reduced recovery of heterozygous mice was observed while backcrossing the null FX allele to C57BL/6J (B6), but was less dramatic in an outcross to CASA/Rk and absent in an outcross to 129S1/SvImJ, indicating that genetic background modifies survival of FX+/- progeny. Substantial strain-specific differences in pre- and postnatal survival of FX-/- progeny were also detected in heterozygous crosses of C57BL/6J congenic, 129S1B6F1, and B6CASAF1 mice. Specifically, intrauterine survival of FX-/- mice was greatly increased during a heterozygous intercross on a uniform C57BL/6J genetic background compared with survival on a hybrid genetic background consisting of a mixture of C57BL/6J and 129S2/SvPas. In addition, statistically significant clustering of FX-/- progeny into litters and specific breeding cages was noted during a B6CASAF1 FX+/- intercross, suggesting a rare mechanism for modifier gene action in which parentally expressed genes define the phenotype, in this case the survival potential, of mutant offspring. Our results disclose that lethality in FX mutant mice is determined by one or more strain-specific modifier loci.

Alleles↗
PubMed1989

Expression characteristics of two potential T cell mediator genes.

T lymphocyte subset-specific cDNA clones were recently isolated by a modified differential screening procedure. The expression patterns of two of these cDNAs, designated as 4-1BB and L2G25B, were studied in greater detail. Nucleotide sequence comparison revealed that 4-1BB was not previously recognized. Although the L2G25B sequence had been recognized recently, the function of the encoded molecule has yet to be well studied. The transcripts of the two cDNAs were inducible by concanavalin A in mouse spleen cells, cloned helper T cells (L2), cloned cytolytic T cells (L3), and cytolytic T cell hybridomas. They were also inducible with stimulation through antigen receptor (TCR), with immobilized anti-TCR antibody in cloned T cells L2, dB45, and L3. Concanavalin A inducibility was inhibited by cyclosporin A. They were not inducible by IL-2 stimulation. The expression patterns of these transcripts were similar to those of IFN-gamma, except that the level of transcripts of the two cDNAs was at least fivefold lower than that of IFN-gamma, and the peak level of expression occurred earlier. These data suggest that L2G25B and 4-1BB may represent new T cell mediators.

Animals↗
PubMed2000

Rapid westernization of children's blood cholesterol in 3 countries: evidence for nutrient-gene interactions?

The aim of this study was to examine potential factors that modify blood cholesterol among children in countries in which dietary and lifestyle habits are becoming westernized. Population data on serum total and lipoprotein cholesterol, anthropometric indexes, and dietary intake were reviewed and compared for children aged 1-18 y from Japan, Spain, and the United States. The data show that total serum cholesterol in Japanese and Spanish children recently exceeded the 75th percentile for US children, primarily reflecting LDL cholesterol, although both LDL and HDL cholesterol contributed. Adiposity indexes do not explain the trends observed. Total and saturated fat intakes increased substantially in both Japan and Spain but in Japan are still lower than intakes in the United States. The Hegsted equation was used to relate differences in serum cholesterol to dietary fat intake. Changes in total serum cholesterol followed established dietary correlations among children in Spain, but not in Japan. Serum cholesterol in Japanese children was predicted to be 0.20-0.32 mmol/L lower than in US children; actual concentrations were considerably higher. These results suggest that a rapid westernization of children's blood cholesterol concentrations has occurred in Japan and Spain. Changes in fat intake predict changes in blood cholesterol in Spain, but not in Japan. Differences in genetic response to diet in certain populations, such as the Japanese, may explain higher blood cholesterol concentrations with lower fat intakes compared with the United States.

Adolescent↗
PubMed2005

In vitro induction of myeloid leukemia-specific CD4 and CD8 T cells by CD40 ligand-activated B cells gene modified to express primary granule proteins.

The primary granule proteins (PGP) of myeloid cells are a source of multiple antigens with immunotherapeutic potential for myeloid leukemias. Therefore, we developed a method to induce T-cell responses to PGP protein sequences. We found that gene-transfected antigen-presenting cells efficiently expand functionally competent PGP-specific CD4 and CD8 T cells. The system was optimized using T-cell responses to autologous CD40-activated B cells (CD40-B) transfected with a cytomegalovirus pp65-encoding expression vector. To generate leukemia-specific T cells, expression vectors encoding the PGP proteinase 3 (PR3), human neutrophil elastase, and cathepsin-G were transfected into CD40-B cells to stimulate post-allogeneic stem cell transplantation T cells from five patients with myeloid and three with lymphoid leukemias. T-cell responses to PGP proteinase 3 and human neutrophil elastase were observed in CD8+ and CD4+ T cells only in patients with myeloid leukemias. T-cell responses against cathepsin-G occurred in both myeloid and lymphoblastic leukemias. T cells from a patient with chronic myelogenous leukemia (CML) and from a posttransplant CML patient, expanded against PGP, produced IFN-gamma or were cytotoxic to the patient's CML cells, demonstrating specific antileukemic efficacy. This study emphasizes the clinical potential of PGP for expansion and adoptive transfer of polyclonal leukemia antigen-specific T cells to treat leukemia.

Antigen-Presenting Cells↗