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PubMed1988

Adriamycin custom-tailored immunoconjugates in the treatment of human malignancies.

Twenty-three patients with disseminated refractory malignancies each received a tailored combination of adriamycin-conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells as tested by immunoperoxidase and flow cytometry. These monoclonal antibodies were then conjugated to Adriamycin and administered intravenously. Seventeen of 23 patients had reactions to the administration of immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus, and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients there was limited antigenic drift among various biopsies within the same patient over time. This observation confirms the necessity for the use of a cocktail of antibodies if one wishes to cover all tumor cells. Preliminary serologic evidence suggests that the development of an IgM antibody, which is specific against the mouse monoclonal antibody, has the specificity and sensitivity to predict clinical reactions. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. In the course of the study free Adriamycin released from the monoclonal antibodies was discovered to be a limiting factor in the amount of antibody that could be administered. Up to 1 g of Adriamycin and up to 5 g of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. This study demonstrates the feasibility and reviews technical considerations in preparing immunoconjugate cocktails for patients with refractory malignancies. The major technical hurdle appears to be the selection of an effective conjugation method that can be used to optimally bind Adriamycin to monoclonal antibodies for targeted cancer therapy.

Animals↗
PubMed1994

Antitumor activity of immunoconjugates composed of boanmycin and monoclonal antibody.

Boanmycin (bleomycin A6, BM), an antitumor antibiotic, was conjugated to monoclonal antibodies including R19, H111 and CCT2. The immunoconjugates exhibited selective cytotoxicity to related target cells including cecum cancer Hce-8693 cells, liver cancer BEL-7402 cells and leukemia CEM cells. They were highly effective against related human tumor xenografts in nude mice, and the inhibition rates by the conjugates were much higher than those by free BM. The inhibition rate by R19-BM conjugate against human cecum cancer xenografts reached 90%. BY immunoelectron microscopy, CCT2-BM conjugate showed specific binding and internalization in leukemia CEM cells. The results indicate that boanmycin-monoclonal antibody immunoconjugates are highly active both in vitro and in vivo.

Adenocarcinoma↗
PubMedDate not supplied

Effects of an anti-CD5 immunoconjugate (CD5-plus) in recent onset type I diabetes mellitus: a preliminary investigation. The CD5 Diabetes Project Team.

Type-I (insulin-dependent) diabetes mellitus is an immunologically mediated disease that results in destruction of the insulin secreting beta cells of the pancreas. T cells have been implicated in the pathogenesis of this disease. One novel form of anti-T-cell therapy is the immunoconjugate CD5-Plus. This agent is composed of the murine IgG1 monoclonal antibody H65, which is directed toward the CD5+ antigen; and ricin A chain, a ribosomal inhibitor protein. We performed a pilot study to evaluate the safety of the immunoconjugate in subjects with type-I diabetes mellitus. We conducted a dose-escalation study using CD5-Plus given as an intravenous infusion for 5 consecutive days. Fifteen subjects (12 men and 3 women) with a mean age of 26 years, a mean duration of diabetes of 4.8 months, and a minimum stimulated C peptide of 0.3 pmol/mL were entered. Six subjects each were treated at the 0.1 and 0.2 mg/kg/day dosage levels, and three subjects were treated at the 0.33 mg/kg/day dose. Glycemic control was determined monthly by recording the glycohemoglobin, total daily insulin requirements, and fasting blood glucoses. Beta-cell function was measured by determining the C-peptide response to a mixed formula meal (Sustacal) at baseline and at 1,3,6,9, and 12 months after treatment. The area under the curve (AUC) of the C-peptide response was calculated and, to reduce variability, related to that of the same subject at baseline. An analysis of subjects who retained at least 80% of their baseline beta-cell function as measured by the AUC was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Therapeutic efficacy of a doxorubicin immunoconjugate in a preclinical model of spontaneous metastatic human melanoma.

Doxorubicin (DOX) was conjugated to a monoclonal antibody (mAb 425) directed against the human epidermal growth factor receptor. The immunoreactivity of these conjugates, with an average of six to eight molecules of DOX per antibody, was largely conserved, and their in vitro cytotoxicity against metastatic human melanoma cells (M24 met) was improved over that of free DOX. An evaluation of the therapeutic efficacy of mAb 425-DOX indicated that this immunoconjugate suppressed the growth of primary and secondary M24 met tumors in mice with severe combined immunodeficiency and prolonged the life span of these animals, whereas an equivalent dose of free DOX was ineffective. Conjugation of DOX to an irrelevant mAb also increased its antitumor effect over that of equivalent amounts of free drug but to a lesser extent than that achieved by the mAb 425-DOX conjugate. These results demonstrate targeted delivery and striking antitumor activity of DOX immunoconjugates in a preclinical model of spontaneous, metastatic human melanoma that was insensitive to free DOX.

Animals↗
PubMedDate not supplied

Ascorbic acid induces lipid peroxidation on neuroectodermal SK-N-LO cells with high endogenous ferritin content and loaded with MAb-ferritin immunoconjugates.

Neuroblasma-and other malignant cells often contain elevated amounts of iron-rich ferritin and H2O2 and may therefore be a potential target for pro-oxidative effects of ascorbic acid (AA), generating cytotoxic products e.g. by lipid peroxidation (LPO). The influence of H2O2 and iron, either in its free form or bound to ferritin, on AA induced LPO was first investigated using erythrocyte ghosts as a model system. Results of these experiments showed that AA induced LPO not only in the presence of free available iron but also in the presence of ferritin. Similarly, AA induced significant LPO in neuroectodermal SK-N-LO cells with elevated intracellular ferritin levels. These LPO promoting effects of ferritin in the presence of AA on SK-N-LO cells could also be observed using ferritin-immunoconjugates: for this purpose, ferritin was bound to human monoclonal antibodies (MAb-ferritin) recognizing ganglioside GD2 which is present in large quantities on cell surfaces of SK-N-LO and many neuroblastoma cells. We conclude that the pro-oxidative effects of AA could be exploited in the treatment of ferritin rich neuroblastoma in combination with chemotherapy or with MAb-ferritin immunoconjugates.

Antibodies, Monoclonal↗
PubMed1997

In vitro and in vivo antitumor activity of immunoconjugates prepared by linking 5-fluorouridine to antiadenocarcinoma monoclonal antibody.

5-Fluorouridine (5-FUr), a cytotoxic antitumoral agent not in clinical use because of its systemic toxicity, and AR-3, a monoclonal antibody specific to a human colorectal adenocarcinoma, were covalently linked via two different strategies. 5-FUr was 5' succinilated after protection of the secondary hydroxyl groups and the carboxylate derivative was then activated as N-hydroxysuccinimidyl ester in order to react with the amino groups present in the monoclonal antibody, giving an amide linkage. Alternatively, a 5-FUr immunoconjugate containing an acid-cleavable hydrazone bond was formed from the reaction between an acyl hydrazide derivative of 5-FUr and a periodate oxydized antibody with approximately 12 aldehyde groups in its carbohydrate region. An average of 9 to 12 drug molecules were attached to the antibody. In a cytotoxic assay on the human colorectal carcinoma cell line HT-29, the hydrazone containing drug conjugate was equally active as the succinylamido conjugate and the free drug. However, ELISA showed that while in the case of the succinylamido conjugate the Mab immunoreactivity was not affected after conjugation, there was a significant loss of reactivity in the acid cleavable conjugate. In a model of a disseminated intraabdominal carcinomatosis by HT-29 intraperitoneal graft in nude mice, the 5-FUr immunoconjugate selected was more effective than the unconjugated drug in medium-term therapy (21 days after the graft and 16 days after drug treatment), albeit in the longer period the efficacy of the two formulations was similar. The toxic effect of the drug-conjugate in vivo was much weaker, demonstrating its clear advantage over the drug, in terms of pharmacological efficacy.

Adenocarcinoma↗
PubMed1996

A double-blind, placebo-controlled study of anti-CD5 immunoconjugate in patients with rheumatoid arthritis. The Xoma RA Investigator Group.

OBJECTIVE: To evaluate the efficacy of an anti-CD5 ricin-linked immunoconjugate (CD5-IC) in patients with rheumatoid arthritis (RA). METHODS: A total of 104 evaluable patients were enrolled in a multicenter, double-blind, multiple-dose, placebo-controlled study of CD5-IC. RESULTS: Treatment with CD5-IC in doses up to 8 mg/m2/day for 4 days in 1 month failed to produce marked or prolonged T cell depletion and was no more effective than placebo in ameliorating disease manifestations. An unexpectedly high placebo response was observed in 48% of the patients. Adverse events were correlated with the dose of CD5-IC, but the treatment was generally well-tolerated. CONCLUSION: At the doses used in this study, CD5-IC was ineffective for treating RA.

Adult↗
PubMed1995

Flow cytometric measurement of NK cell immunoconjugates by pulse width processing.

Pulse width analysis, in flow cytometry, has been widely used for optimal cell size resolution in cell kinetics analysis. Pulses, generated by scattered light or fluorescence of cells, are electronically analyzed for their height and width. The information generated from these two properties of the pulses is utilized to distinguish signals from single cells vs. signals from cell clumps or aggregates. Pulse width, unlike pulse height, is more sensitive to differences in cell diameter, and therefore can discriminate very small differences in it, which pulse height cannot. We have exploited this property of pulse widths to measure immunoconjugates between NK cells and their targets. Discrimination of the free target cells from the conjugated ones is possible by the pulse widths of only light scatter signals, both forward and/or orthogonal. This resolution was not obtained if pulse height of the same signals was visualized. Using this resolution it was possible to distinguish single cells from the aggregates between target and effector cells. We propose that this is a better method for distinguishing conjugates than the method in which prior vital staining of cells is used.

Animals↗
PubMed2006

Direct electrochemical immunoassay based on a silica nanoparticles/sol-gel composite architecture for encapsulation of immunoconjugate.

A highly hydrophobic and non-toxic colloidal silica nanoparticle/polyvinyl butyral sol-gel composite membrane was prepared on a platinum wire electrode. With diphtheria-toxoid (D-Ag) as a model antigen and encapsulation of diphtheria antibody (D-Ab) in the composite architecture, this membrane could be used for reagentless electrochemical immunoassay. It displayed a porous and homogeneous composite architecture without the aggregation of the immobilized protein molecules. The formation of immunoconjugate by a simple one-step immunoreaction between D-Ag in sample solution and the immobilized D-Ab introduced the change in the potential. Under optimal conditions, the D-Ag analyte could be determined in the linear ranges from 10 to 800 ng ml(-1) with a relatively low detection limit of 2.3 ng ml(-1) at 3delta. The D-Ag immunosensor exhibited good precision, high sensitivity, acceptable stability, accuracy, and reproducibility. This composite membrane could be used efficiently for the entrapment of different biomarkers and clinical applications.

Antigens, Bacterial↗
PubMed2003

A phase 2 study of the cytotoxic immunoconjugate CMB-401 (hCTM01-calicheamicin) in patients with platinum-sensitive recurrent epithelial ovarian carcinoma.

The compound CMB-401 is an immunoconjugate consisting of the monoclonal antibody (MAb) hCTM01 directed against polymorphic epithelial mucin covalently bound to the cytotoxic antibiotic calicheamicin by an amide linker. We evaluated CMB-401 as monotherapy for the treatment of recurrent platinum-sensitive epithelial ovarian carcinoma (EOC). Twenty-one 21 women aged 38 to 80 years with recurrent EOC (recurrence >6 months after initial platinum-containing chemotherapy) were enrolled. Tumor response and serum cancer antigen 125 (CA125) levels were assessed before and after active treatment. After an initial intravenous (i.v.) dose of hCTM01 (without calicheamicin), the calicheamicin-linked CMB-401 (16 mg/m(2 ) i.v.) was administered over 60 min for up to 7 cycles, with 4 weeks between cycles. Nineteen patients were evaluable. Measurable changes observed following administration of CMB-401 did not meet the criteria for partial remission (PR). CMB-401 was not effective as monotherapy for this type of EOC. Adverse events experienced by patients in the study included nausea (95%), asthenia (90%), abdominal pain (62%), headache (57%), anorexia (57%), and diarrhea (57%), mostly at a toxicity grade level of 1 or 2. Based on published efficacy of conjugates that deliver calicheamicin via hybrid (bifunctional) linkers [e.g. gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia], we hypothesize that the amide linker used in CMB-401 may have contributed to its failure to induce PR in patients in this study. Use of hybrid linkers to target hCTM01 or other antibodies to EOC may warrant further investigation.

Adult↗
PubMed1997

Disposition of conjugate-bound and free doxorubicin in tumor-bearing mice following administration of a BR96-doxorubicin immunoconjugate (BMS 182248).

PURPOSE: The chimeric BR96-doxorubicin (DOX) immunoconjugate, BMS 182248, has induced remissions and cures of human lung adenocarcinoma (L2987) implanted in athymic mice. The purpose of this study was to evaluate the biodistribution of DOX after BMS 182248 administration to tumor-bearing mice and to evaluate the ability of BMS 182248 to target DOX to tumors. METHODS: For this evaluation, L2987-implanted mice were given BMS 182248 (5 mg DOX/kg; three doses 4 days apart) and the levels of both conjugate-bound and free DOX in plasma, tumor, liver and heart were determined. RESULTS: Conjugate-bound DOX comprised the majority of plasma DOX, with relatively low levels of free DOX present. From plasma, conjugate-bound DOX distributed to the tissues examined with the order of concentration (per gram of tissue) being tumor > liver > heart. Free DOX was also detected in liver and heart, but at concentrations lower than those present after an equivalent DOX dose (5 mg/kg; three doses 4 days apart). The total exposure of heart to free DOX after BMS 182248 administration was about one-quarter of that found after the administration of DOX alone. The elimination kinetics of both conjugate-bound and free DOX from heart and liver after BMS 182248 administration paralleled those observed from plasma, indicating that equilibrium had been attained between these nontumor tissues and plasma. The elimination kinetics of both entities from tumors, however, were different from those from plasma, liver and heart. BMS 182248 produced sustained levels of both conjugate-bound and free DOX which were present throughout the experiment. This suggested that, in contrast to normal tissues, tumor tissue retention of BMS 182248 by antigen-promoted binding had occurred and that kinetics of free DOX in the tumors were controlled by the rate of release of DOX from tumor-associated BMS 182248. As a result of this retention, the tumor concentrations of free DOX after BMS 182248 administration exceeded those produced by i.v. administration of DOX at the same dose, a finding consistent with the greater antitumor activity of BMS 182248 relative to DOX. BMS 182248 also liberated DOX upon incubation with rat liver lysosomes and was accumulated by L2987 cells in culture, with the subsequent intracellular release of DOX. CONCLUSIONS: BMS 182248 effectively delivered DOX to L2987 xenografts implanted in athymic mice and produced higher and more prolonged tumor concentrations of free DOX than the administration of DOX alone. Following BMS 182248 administration, normal tissues (liver and heart) were exposed to lower overall concentrations of free DOX than were produced by administration of an equivalent DOX dose.

Adenocarcinoma↗
PubMed1995

In vitro and in vivo evaluation of streptavidin immunoconjugates of the second generation TAG-72 monoclonal antibody CC49.

Streptavidin was conjugated to the second-generation TAG-72 monoclonal antibody CC49 at lysine amino acids, oxidized carbohydrates or reduced disulfides on the immunoglobulin. The streptavidin immunoconjugates were radiolabelled with 111In-DTPA-biocytin and their immunological characteristics evaluated in vitro and in vivo. FPLC analysis showed a single peak (mol. wt > 350 kDa) for the lysine conjugate and sulfhydryl conjugate (mol. wt approximately 210 kDa) but multiple peaks (approximately 210 to > 350 kDa) for the carbohydrate conjugate. There were only small differences in immunoreactivity against bovine submaxillary mucin in vitro. However, in mice bearing subcutaneous LS174T tumours, the lysine conjugate exhibited significantly lower tumour uptake (< 2% i.d./g) compared to the other streptavidin-CC49 conjugates (10-40% i.d./g) or DTPA-CC49 (14-18% i.d./g). Due to the monomeric nature and smaller molecular size of the sulphhydryl conjugate, and its similar in vitro and in vivo characteristics compared with DTPA-CC49, this conjugate has been selected for future pretargeting studies with 111In and 90Y biotin.

Animals↗
PubMed2005

A gold nanoparticles/sol-gel composite architecture for encapsulation of immunoconjugate for reagentless electrochemical immunoassay.

A highly hydrophilic, non-toxic and conductive colloidal gold nanoparticle/titania sol-gel composite membrane with a low contact angle was prepared on a glassy carbon electrode via a vapor deposition method. With human chorionic gonadotrophin (hCG) as a model antigen and encapsulation of horseradish peroxidase-labeled hCG antibody (HRP-anti-hCG) in the composite architecture, this membrane could be used for reagentless electrochemical immunoassay. It displayed a porous and homogeneous composite architecture without the aggregation of the immobilized protein molecules. The presence of gold nanoparticles provided a congenial microenvironment for adsorbed biomolecules and decreased the electron transfer impedance, leading to a direct electrochemical behavior of the immobilized HRP. The formation of immunoconjugate by a simple one-step immunoreaction between hCG in sample solution and the immobilized HRP-anti-hCG introduced a barrier of direct electrical communication between the immobilized HRP and the electrode surface. Under optimal conditions, the hCG analyte could be determined in two linear ranges from 0.5 to 5.0 mIU/mL and 5.0 to 30 mIU/mL with a relatively low detection limit of 0.3 mIU/mL at 3sigma. The hCG immunosensor exhibited good precision, high sensitivity, acceptable stability, accuracy and reproducibility. This composite membrane could be used efficiently for the entrapment of different biomarkers and clinical applications.

Biomarkers↗
PubMed2007

Cellular penetration and nuclear importation properties of 111In-labeled and 123I-labeled HIV-1 tat peptide immunoconjugates in BT-474 human breast cancer cells.

INTRODUCTION: Our objective was to compare the cell penetration and nuclear importation properties of 111In-labeled and 123I-labeled immunoconjugates (ICs) composed of 16-mer peptides (GRKKRRQRRRPPQGYG) derived from HIV-1 transactivator of transcription (tat) protein and anti-mouse IgG (mIgG) in BT-474 breast cancer (BC) cells. METHODS: [111In]tat ICs were constructed by site-specific conjugation of tat peptides to NaIO4(-)-oxidized carbohydrates in the Fc domain of diethylenetriaminepentaacetic-acid-modified anti-mIgG antibodies. Immunoreactivity against mIgG was assessed in a competition assay. The kinetics of the accumulation of [111In]anti-mIgG-tat IC and [123I]anti-mIgG-tat ICs in BT-474 cells and the elimination of radioactivity from cells, cytoplasm or nuclei were determined. The effects of excess tat peptides or NH4Cl (an inhibitor of endosomal acidification) on cellular uptake and nuclear importation of [111In]anti-mIgG-tat were measured. RESULTS: [111In]anti-mIgG-tat was >97% radiochemically pure and exhibited preserved immunoreactivity with mIgG epitopes. [123I]Anti-mIgG-tat penetrated BT-474 cells more rapidly than [111In]anti-mIgG-tat ICs and achieved a 1.5-fold to a 2-fold higher uptake in cells and nuclei. Cell penetration and nuclear uptake of [111In]anti-mIgG-tat were inhibited by excess tat peptides and NH4Cl. Elimination of radioactivity from BT-474 cells and nuclei was more rapid and complete for 123I-labeled than for 111In-labeled anti-mIgG-tat ICs. CONCLUSION: Tat peptides derived from HIV-1 tat protein promoted the penetration and nuclear uptake of radioactivity following the incubation of 111In-labeled and 123I-labeled anti-mIgG antibodies with BT-474 human BC cells. 111In-labeled tat ICs are feasible for inserting radionuclides into cancer cells with potential for targeting intracellular and, particularly, nuclear epitopes for imaging and/or radiotherapeutic applications.

Breast Neoplasms↗
PubMed2002

Affinity chromatography and co-chromatography of bispecific monoclonal antibody immunoconjugates.

Bispecific monoclonal antibodies (bsMAb) are unique macromolecules functioning as cross-linkers with two different predetermined binding specificities. A wide range of potential applications employing these probes can be envisioned in immunodiagnostics and immunotherapy. One of the major limitations for the use of bsMAbs produced by hybrid-hybridomas is the production of parental monospecific antibodies along with bsMAbs. Hence, the purification of desired bsMAb free from both parental mAbs and other possible promiscuous combinations is essential. Purification of antibodies is the single greatest obstacle in obtaining an immunoprobe with high specific activity. This review describes the affinity purification and affinity co-purification techniques for the separation of bsMAb as a pre-formed immune complex or as a pure species. The use of immobilized ligands is the basis of affinity chromatography. Affinity chromatography can be classified into three different categories depending on the properties of the immobilized ligand. The ligand-specific affinity chromatography is based on the extremely specific immobilized ligand, directed towards the protein or antibody of interest. Using a dual, sequential affinity chromatography, bsMAb can be purified from a mixture of bispecific and monospecific monoclonal antibodies with a ligand specific for each antibody. Thiophilic adsorption is a group-specific affinity method that can be successfully used to separate monospecific forms from bispecific species by salt gradient elution. Affinity co-chromatography offers a convenient one-step method for purification of bulk amounts of immunoconjugates for diagnostic applications by exploiting several dye-ligands known to bind certain enzymes. The same method could be potentially used for quality control and quality assurance purposes in industrial biotechnology.

Antibodies, Bispecific↗
PubMed2001

Combination chemotherapy and photodynamic therapy of targetable N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin/mesochlorin e(6)-OV-TL 16 antibody immunoconjugates.

The aim of this study was to evaluate the combination chemotherapy and photodynamic therapy of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound doxorubicin (DOX) and mesochlorin e(6) (Mce(6)) targeted with an OV-TL 16 monoclonal antibody (P-DOX-Ab and P-Mce(6)-Ab, respectively) in nude mice bearing human ovarian OVCAR-3 carcinoma xenografts. P-DOX-Ab and P-Mce(6)-Ab were synthesized by first conjugating DOX or Mce(6) to an HPMA copolymer precursor (Mw=21000), then reacting with OV-TL 16 antibody. The immunoconjugates were purified by size exclusion chromatography on Superose 6 column and analyzed. The Mce(6) concentration in tissues was determined by a fluorescence assay. Eighteen hours after administration, the tumors received a light dose of 220 J/cm(2) from a KTP 650-nm dye-laser. P-DOX-Ab and P-Mce(6)-Ab had polymer:drug:protein weight ratios of 32:3:62 and 26:2:72, corresponding to polymer:drug:protein molecular ratios of approximately 4:14:1 and 3:8:1, respectively. The biodistribution results indicated that the percentage of total administered dose of Mce(6) in tumors reached approximately 1% for the nontargeted conjugate at 18 h after administration, while that of P-Mce(6)-Ab was approximately 13 times higher. Nude mice bearing OVCAR-3 xenografts that received one i.v. dose of P-DOX-Ab (2.2 mg/kg DOX equivalent) and P-Mce(6)-Ab (1.5 mg/kg Mce(6) equivalent) with light irradiation achieved a xenograft cure rate of more than 60%. The incorporation of OV-TL 16 antibody dramatically enhanced the accumulation in tumors with a concomitant increase in the therapeutic efficacy of P-DOX-Ab and P-Mce(6)-Ab in combination therapy, which may probably be attributed to both antibody targeting and enhanced permeability and retention (EPR) effects.

Animals↗
PubMed1997

Are immunoconjugates useful for therapy with autoimmune diseases?

Immunoconjugates or immunotoxins (ITs) are targeting molecules which consist of a monoclonal antibody together with a toxin--thereby they can selectively kill target cells in a highly efficient manner. The use of ITs as a drug targeting approach is one of the most attractive research fields for tumor therapy; however, the study of ITs for the treatment of autoimmune diseases has been given little attention until recently. It has been shown that ITs could help alleviate the symptoms of myasthenia gravis and rheumatoid arthritis in animal models. In the last 3 yr ITs have been used in clinical trials (phase I and phase II) for the treatment of various autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus and psoriasis. This article reviews the main progress on the application of ITs for the therapies of autoimmune diseases. The preliminary results suggest the future may hold some promise, but side effects, in addition to there being no convincing efficacy, remain unresolved.

Animals↗
PubMed1997

The potential for immunoconjugates in lymphoma therapy.

Contemporary combination chemotherapy offers curative treatment for 30% to 50% of patients with advanced-stage, aggressive non-Hodgkin's lymphomas (NHL). However, conventional therapies cure few patients with indolent lymphomas or relapsed lymphomas of any histology. Myeloablative chemoradiotherapy with bone marrow or stem cell transplantation can provide pro-longed disease-free survival for a minority (20% to 50%) of patients with relapsed NHL, but new treatment approaches are clearly needed. In recent years, several groups of investigators have provided preliminary evidence suggesting that monoclonal antibodies (mAbs), in unmodified form or conjugated to toxins, drugs, or radioisotopes, may offer another effective therapeutic modality for patients with relapsed lymphomas. This article reviews current immunotherapy of NHL using antibody immunoconjugates.

Animals↗