Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Immunoconjugates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed2004

Immunobiologic therapies for myelodysplastic syndrome.

Recent progress in understanding the pathobiology of the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have led to the development of various immunologically oriented therapies for these diseases. The existence of elevated levels of tumor necrosis factor-alpha (TNF-alpha) in bone marrow during early stages of MDS, and the possibility that TNF- proportional, variant suppresses normal hematopoiesis led to studies of attempts to block the activity of TNF-alpha. An anti-TNF monoclonal antibody and an antibody comprised of the soluble extracellular ligand-binding portion of the TNF receptor have both been evaluated recently in several small pilot studies. The recognition that marrow suppression in MDS may, in part, be a T-cell mediated autoimmune process has stimulated various trials of antithymocyte globulin and other similar agents. Gemtuzumab ozogamicin, an antibody against CD33 conjugated to the cytotoxic agent calicheamicin, is approved for use in AML and is currently being investigated as a potential therapeutic agent in MDS. Clinical trials were conducted as either monotherapy or in combination with cytokines such as IL-11 and chemotherapeutic agents including idarubicin, fludarabine, and/or cytarabine. Other antibodies are being developed as immunoconjugates with radioisotopes as part of conditioning regimens prior to bone marrow transplantation for AML or MDS. These include (131)I-anti-CD45 antibody (BC8), (131)I anti-CD33 antibody (p67), (213)Bi-M195 antibody, and (188)Re-labeled anti-CD66 antibody. The clearest example of successful immunotherapy for MDS (and AML) is the use of the graft-versus-tumor effect associated with allogeneic hematopoietic cell transplantation. Recently, nonmyeloablative transplants have been explored with encouraging results. Vaccines using overexposed self-antigens such as WT1 and PR1 are other attempts to induce a T-cell mediated response against MDS.

Animals↗
PubMed2006

New agents for the treatment of acute myeloid leukemia.

The heterogeneity of acute myeloid leukemia (AML) has been established by many new insights into the diagnosis, pathogenesis, clinical manifestations, treatment, and prognosis of patients with AML. Morphology remains the foundation for the diagnosis. However, additional diagnostic studies, including immunophenotyping, cytogenetic evaluation, and molecular genetic studies, are necessary to develop treatments because specific subtypes of AML can now be approached with targeted therapy. Acute promyelocytic leukemia (APL), defined by a single molecular abnormality, is now treated with specific targeted therapy, all-trans retinoic acid (ATRA), and this subtype of AML is now highly curable. Currently, a number of agents have been explored in AML, including anti-CD33 antibodies and immunoconjugate drugs, inhibitors of multidrug resistance proteins, farnesyl transferase inhibitors, tyrosine kinase inhibitors, anti-Bcl-2 transcription agents, and inhibitors of mammalian target of rapamycin (mTOR). New alkylating agents, and purine analogs such as Cloretazine and clofarabine, affect DNA and ribonucleoside reductases, respectively. These agents have shown promise in small studies. Large phase III studies will address whether these are effective in inducing complete responses. Combining targeted agents with chemotherapy may improve the response rates. The plan for the future is to find therapeutic strategies that are specific for patients based on the specific biology of the disease. Future studies will investigate combinations of targeted therapies with each other and with chemotherapies to maximize the inhibition of multiple pathways present in AML. Additionally, evaluation of the identified prognostic factors and gene mutations will enable further pathologic classification of patients with AML.

Antineoplastic Agents, Alkylating↗
PubMed2004

Investigations using immunization to attenuate the psychoactive effects of nicotine.

Despite the enormous health risks, people continue to smoke and use tobacco primarily as a result of nicotine addiction. As part of our immunopharmacotherapy research, the effects of active and passive immunizations on acute nicotine-induced locomotor activity in rats were investigated. To this end, rats were immunized with either a NIC-KLH immunoconjugate vaccine designed to elicit an antinicotine immune response, or were administered an antinicotine monoclonal antibody, NIC9D9, prior to a series of nicotine challenges and testing sessions. Vaccinated rats showed a 45% decrease in locomotor activity compared to a 16% decrease in controls. Passive immunization with NIC9D9 resulted in a 66.9% decrease in locomotor activity versus a 3.4% decrease in controls. Consistent with the behavioral data, much less nicotine was found in the brains of immunized rats. The results support the potential clinical value of immunopharmacotherapy for nicotine addiction in the context of tobacco cessation programs.

Animals↗
PubMed2004

Synthesis of potent taxoids for tumor-specific delivery using monoclonal antibodies.

The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prepared to investigate the most suitable position for conjugation. A second series of taxoids modified at the C-2 position aimed at increasing the potency of these taxanes has also been prepared.

Antibodies, Monoclonal↗
PubMed2004

Epidermal growth factor receptor: a promising target in solid tumours.

The epidermal growth factor receptor (EGFR) is expressed in a wide variety of solid tumours. It has been demonstrated that the EGFR-associated signaling pathway plays an important role in carcinogenesis and cancer progression. In the new therapeutic paradigm of molecular-targeted cancer therapy, interference with intracellular signaling cascades is an appealing treatment approach. Inhibitory strategies under study include monoclonal antibodies, tyrosine kinase inhibitors, EGFR-ligand conjugates, EGFR immunoconjugates, and antisense oligonucleotides. Many of these strategies have demonstrated efficacy against EGFR-expressing tumour cells in preclinical studies, prompting a large number of clinical trials. In particular, clinical studies using monoclonal antibody blockade and EGFR tyrosine kinase inhibitors have suggested that EGFR blockade is a well-tolerated and effective treatment strategy; however, more trials are needed to precisely define how these agents will fit into modern cancer care.

Animals↗
PubMed2006

Monoclonal antibodies in the treatment of lung cancer.

BACKGROUND: Lung cancer is an aggressive disease and its conventional therapy is far from success. There is a strong need for new, better approaches to improve survival, symptom control and quality of life. METHODS: The authors searched the literature for indexed articles published over the past 30 years from Pubmed concentrating on all possibilities of monoclonal antibodies in the therapy of tumours and especially of lung cancer. RESULTS: The search resulted in more then 200 published articles. Important major reports of the pre-clinical/clinical investigations of monoclonal antibodies in the therapy of tumours, with an emphasis on lung cancer were reviewed, screened and tracked for other relevant publications and the yielded data were summarized and systematized. CONCLUSION: It is concluded, that immunotherapy and the reviewed use of monoclonal antibodies in the therapy of tumours (including lung cancer) certainly carries a hope. However, studies of this topic are in a wide range of phases, from experiments to clinical trials, thereby their results are not comparable with each other. Based on the data available though the authors feel that active immunization with monoclonal antibodies as anti-idiotype vaccines, and antibody targeting with immunoconjugates (immunotoxins, radioimmunoconjugates and chemoimmunoconjugates) are the most promising methods. Radioimmunoguided surgery and immunoguided focal ablation are also valuable. Anti-growth factor monoclonal antibodies are the most evaluated agents so far. They certainly have an objective effect, though they are still not the 'magic bullets', waited for by many clinicians. The use of monoclonal antibodies against the escape mechanisms of tumours can be a good auxiliary method. There are too little data on the value of antibodies directly targeting tumour cells and on combined passive immunotherapy. Due to constant research, other modalities, such as prodrug activation, T cell activation, the use of intrabodies, T bodies, and conjugated antibody fragments might also prove to be valuable.

Antibodies, Monoclonal↗
PubMed2006

Management of high risk metastatic prostate cancer: the case for novel therapies.

PURPOSE: We reviewed the results of preliminary studies of select novel agents for metastatic prostate cancer and discuss the potential benefit of these agents for earlier stage disease, eg biochemically recurrent prostate cancer with high risk features. MATERIALS AND METHODS: Available data on select investigational immunotherapies as well as endothelin-A receptor antagonists and survivin inhibitors were obtained and reviewed through PubMed searches, conference proceedings and unpublished proprietary information, when available. RESULTS: A large number of promising agents are in varying stages of development. Phase III results have been reported for the endothelin-A receptor antagonist atrasentan. Several immunotherapies are currently in phase II/III trials, namely the GM-CSF transduced tumor cell vaccine GVAX, the prostatic acid phosphatase loaded dendritic cell vaccine Provenge and the prostate specific antigen expressing poxvirus vaccine PROSTVAC-VF. Another immunotherapy, the prostate specific membrane antigen immunoconjugate MLN2704 (Millennium Pharmaceuticals, Cambridge, Massachusetts), is in phase I/II study. The first clinical inhibitors of survivin are in early phase I studies. Several of these agents, including atrasentan, have shown statistically significant but modest effects in the advanced disease setting in which they have been studied. CONCLUSIONS: Clinical trial design with these novel therapies presents particular challenges since most of these agents may induce disease stabilization rather than disease regression. There is a risk of false-negative results and failure to recognize a potentially efficacious agent if these cytostatic agents are studied only in men with advanced, heavily pretreated disease in whom life expectancy is measured in months. We advocate the early referral and enrollment of men with high risk prostate cancer in clinical trials.

Antineoplastic Agents↗
PubMed2004

Drug delivery systems for vitreoretinal diseases.

The eye has an environment that is specific unto itself in terms of pharmacokinetics: the inner and outer blood-retinal barriers separate the retina and the vitreous from the systemic circulation and vitreous body, which physiologically has no cellular components, occupies the vitreous cavity, an inner space of the eye, and reduces practical convection of molecules. Considering this, development of a drug delivery system (DDS) is becoming increasingly important in the treatment of vitreoretinal diseases not only to facilitate drug efficacy but also to attenuate adverse effects. The DDS has three major goals: enhances drug permeation (e.g., iontophoresis and transscleral DDS), controls release of drugs (e.g., microspheres, liposomes, and intraocular implants), and targets drugs (e.g., prodrugs with high molecular weight and immunoconjugates). Comprehensive knowledge of these should lead to development of innovative treatment modalities.

Absorbable Implants↗
PubMed2005

Hairy cell leukemia: survival and relapse. Long-term follow-up of purine analog-based therapy and approach for relapsed disease.

Since its initial description approximately 50 years ago, there has been an impressive evolution in therapies for hairy cell leukemia. Long-term follow-up with 2-cholorodeoxyadenosine and 2'-deoxycoformycin demonstrates that both agents result in a high complete remission rate and overall survival. Relapse rates appear to be between 20% and 30%. Therapeutic strategies for patients with relapsed disease include retreatment with a purine analog, rituximab, or the anti-CD22 pseudomonas exotoxin A immunoconjugate, BL-22.

ADP Ribose Transferases↗
PubMed1993

Radioimmunoconjugates in the detection of infection and inflammation.

Various nuclear medicine techniques are widely used to image foci of infection and inflammation. Among the relatively new radiopharmaceuticals for this purpose are radioimmunoconjugates such as labeled murine monoclonal antigranulocyte antibodies and labeled human polyclonal nonspecific immunoglobulin G. This article reviews some background information, mechanism of action, side effects, biodistribution, kinetics, results of clinical studies, and dosimetry of several radioimmunoconjugates both of murine monoclonal and human polyclonal origin. The efficacy of these agents has been demonstrated in a variety of clinical conditions. Radiolabeled immunoconjugates may emerge as convenient alternatives to the present technique of choice: in vitro blood cell labeling techniques with their inherent problems and risks.

Humans↗
PubMed1992

Penetration of macromolecules into contracted blood clot.

The effectiveness of thrombolytic therapy is determined by accessibility of thrombus compartments to plasminogen activators and, therefore, depends on permeability of thrombus to blood born macromolecules. Accumulation of 125I labeled proteins with molecular massess ranging from 150 to 450 kD into partly contracted blood clot or plasma clot was consistent with diffusion coefficients 3.2 x 10(-11) and 2.7 x 10(-11) m2 s-1, respectively. So far as the model conditions imitated those for venous thrombi, these data indicate that such thrombi are porous enough for immunoconjugates of relatively big size.

Animals↗
PubMed1995

Dynamics of photoinduced cell plasma membrane injury.

We have developed a video microscopy system designed for real-time measurement of single cell damage during photolysis under well defined physicochemical and photophysical conditions. Melanoma cells cultured in vitro were treated with the photosensitizer (PS), tin chlorin e6 (SnCe6) or immunoconjugate (SnCe6 conjugated to a anti-ICAM monoclonal antibody), and illuminated with a 10 mW He/Ne laser at a 630 nm wavelength. Cell membrane integrity was assessed using the vital dye calcein-AM. In experiments in which the laser power density and PS concentration were varied, it was determined that the time lag before cell rupture was inversely proportional to the estimated singlet oxygen flux to the cell surface. Microscopic examination of the lytic event indicated that photo-induced lysis was caused by a point rupture of the plasma membrane. The on-line nature of this microscopy system offers an opportunity to monitor the dynamics of the cell damage process and to gain insights into the mechanism governing photolytic cell injury processes.

Cell Line↗
PubMed2004

Killing of target cells by redirected granzyme B in the absence of perforin.

Granzyme B (GzmB) is a potent apoptosis-inducing serine protease of cytotoxic lymphocytes. Following receptor-mediated endocytosis, GzmB is supposed to enter the cytosol through perforin-mediated membrane disruption. We investigated whether retargeting of GzmB to Lewis Y positive surface receptors could lead to perforin-independent target cell death. We coupled recombinant GzmB to the Lewis Y-binding antibody dsFv-B3. Targeting of GzmB to Lewis Y positive cells triggered cell death with similar efficacy as dsFv-B3 targeted Pseudomonas exotoxin fragment 38 (PE38). Since GzmB was only weakly inhibited by plasma proteins, GzmB-based immunoconjugates should be useful as a new class of immunotoxins with low immunogenicity utilizing programmed cell death for therapeutic purposes.

Animals↗
PubMed1999

Production of an immunoenzymatic tracer combining a scFv and the acetylcholinesterase of Bungarus fasciatus by genetic recombination.

We constructed a plasmid containing a chimeric gene composed of the gene encoding acetylcholinesterase (AChE) from Bungarus fasciatus venom and a gene encoding a single chain antibody fragment (scFv) directed against one of the two subunits of a presynaptic neurotoxin from rattlesnake. Large quantities of the fusion protein were produced in the culture medium of transfected COS cells. Fusion to AChE did not affect the ability of the scFv to recognise its antigen. Similarly, the AChE activity was not impaired in the fusion. The fusion protein was purified from the culture medium in a single step by affinity chromatography. The immunoconjugate obtained consisted of a soluble monomeric form of AChE fused to scFv. It was monovalent and had a molecular weight of 94 kDa. The properties of this scFv-AChE fusion show that the simple, reproducible preparation of various recombinant monovalent immunoenzymatic tracers with low molecular weight is possible. In addition, in the construct presented, the scFv domain can be easily changed to another one taking advantage of the SfiI-NotI restriction sites surrounding this domain.

Acetylcholinesterase↗
PubMed2003

Experimental comparison of three monoclonal antibodies for the class-selective immunoextraction of triazines. Correlation with molecular modeling and principal component analysis studies.

The specificity of three immunosorbents (ISs) based on different monoclonal anti-triazine antibodies has been characterized by extraction recoveries studies and with step elution experiments. Both indicated that the anti-dichloroatrazine IS is specific of terbutylazine and cyanazine. The anti-atrazine IS is specific of the chlorotriazines, whereas the anti-ametryn IS can trap all the triazines. This confirms the great influence of the hapten design on the specificity of the resulting antibodies, even if the target molecules are small. Moreover, the anti-ametryn IS is suitable for class-selective extraction of triazines contained in complex matrices. An approach designed to learn more about the specificity for a group of structurally related compounds of antibodies produced with a given compound is proposed and evaluated. Molecular modeling followed by principal component analysis has been used to obtain distribution maps with the relative position of each immunoconjugate and all the triazines. In all three cases, conclusions on specificity made with the analysis of the maps fit well with the experimental results. Consequently, molecular modeling coupled with principal component analysis seems to be a unique, inexpensive, and rapid tool to select the appropriate hapten providing highly specific or class-specific antibodies according to the given problem.

Antibodies, Monoclonal↗
PubMed1998

An ELISA to determine the biodistribution of human monoclonal antibody in tumor-xenografted SCID mice.

An ELISA technique was developed to assay the distribution of native human monoclonal antibodies (mAbs) in tumor-xenografted SCID mice. This was used in an investigation of its potential as an alternative to the conventional radioisotopic technique for mAb biodistribution assays which would be simpler to implement and might yield results in closer accord with actual mAb activity because it is based on the use and detection of the native mAbs rather than their radioisotope-coupled immunoconjugates. SCID mice bearing xenografted tumors of the human lung adenocarcinoma cell line A549 received injections via the tail vein of four human mAbs that had been obtained from human-mouse heterohybridomas and were known to be reactive with A549. The biodistribution of the mAbs was assayed by the ELISA technique seven days after the mAb injection. The assay yielded tumor/serum ratios for the four reactive mAbs which were in the range of three to six and tumor mAb levels which were in the range of 0.28 to 0.92 %ID/g (percent of injected mAb dose per gram of tumor). The tumor mAb levels were thus lower than the levels commonly found by radioisotopic assay, and further investigation is desirable to determine the cause of the difference. The results indicate that ELISA can provide a simple, practical means of investigating the biodistribution of human mAbs in mice bearing xenografted carcinomas. The application of this procedure would obviate the need for the complex facilities and procedures associated with radioisotopic labelling and assay.

Adenocarcinoma↗
PubMed1994

Radioimmunoscintigraphy with 111indium labeled CYT-356 for the detection of occult prostate cancer recurrence.

We assessed the safety and ability of the 111indium labeled immunoconjugate 7E11-C5.3-glycyl-tyrosyl-(N,e-diethylenetriaminepentaacetic acid)-lysine (CYT-356) to detect sites of occult prostate cancer in 27 subjects who had undergone radical prostatectomy and whose only evidence of recurrent disease was an increasing (0.8 ng./ml. or greater) serum prostate specific antigen (PSA). All subjects underwent whole body scintigraphy between 2 and 4 days following the radiopharmaceutical injection. Routine blood work and human anti-mouse antibody titers were monitored. Scintigraphic findings were compared with clinical parameters, prostatic fossa biopsy results and conventional imaging techniques. Except for transient hypotension in 1 subject following the second infusion, no side effects or human anti-mouse antibody titers were detected. In 22 subjects 1 or more lesions were detected, of which 11 (50%) were confirmed by biopsy, computerized tomography or magnetic resonance imaging. Of 14 subjects with lesions in the prostatic fossa 13 had biopsies performed, 8 (62%) of which were positive. Magnetic resonance imaging confirmed tumor in the spine and chest computerized tomography findings were compatible with lesions seen in the mediastinum in 1 subject each. There was a statistically significant relationship between detecting a scan abnormality and the initial pathological stage of disease but not with the serum PSA. These data provide preliminary evidence that 111indium labeled CYT-356 can be safely administered and readministered, and it detects sites of occult prostate cancer recurrence in subjects whose PSA is increasing following radical prostatectomy.

Humans↗
PubMed2000

Indium-111 capromab pendetide (ProstaScint) uptake in neurofibromatosis.

We report on the demonstration of nonspecific accumulation of indium-111 capromab pendetide (ProstaScint) in neurofibromas in a patient with a rising prostate-specific antigen level after prostatectomy. Although the immunoconjugate is targeted to a specific membrane antigen present in human prostate carcinoma, nonspecific uptake can occur in other entities. Indium-111 capromab pendetide scintigraphy is a valuable diagnostic tool that should always be interpreted within the context of the clinical history and the laboratory and radiologic findings to avoid misinterpretation.

Antibodies, Monoclonal↗