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At least 109 records · Page 6Linked to original sources
PubMed2001

[Antitumor effect of lidamycin-containing monoclonal antibody immunoconjugate with downsized-molecule].

OBJECTIVE: To develop a novel monoclonal antibody (mAb) immunoconjugate with downsized-molecule and highly potent antitumor effects. METHODS: The mAb conjugate was prepared by linking lidamycin (LDM), an antitumor antibiotic with extremely potent cytotoxicity, to mAb Fab' fragment. The molecular weight of Fab'-LDM was determined by non-reduced SDS-PAGE. The immunoreactivity of Fab'-LDM conjugate with cancer cells was detected by ELISA. The antitumor activity of the conjugate was determined by MTT assay, clonogenic assay, and animal model of transplantable colon carcinoma 26' (C26) in mice. RESULTS: The relative molecular mass of Fab'-LDM conjugate was approximately 65,000, suggesting a molar ratio of 1:1 between Fab' fragment and LDM in the conjugate. Fab'-LDM was reactive with hepatoma BEL-7402 and colon carcinoma 26 cells, but not reactive with KB cells. The cytotoxicity of Fab'-LDM conjugate to BEL-7402 cells, the antigen relevant cancer cells, was 13-fold more potent than that of free LDM, while the cytotoxicity of Fab'-LDM conjugate against C26 cells was 5.5-fold more potent than that of free LDM. However, the cytotoxicity of Fab'-LDM conjugate to KB cells, the antigen irrelevant cells, was similar to that of free LDM. Given by 3 intravenous injections, on day 1, 4 and 7, Fab'-LDM conjugate at doses of 0.05 mg/kg, 0.1 mg/kg and 0.2 mg/kg markedly suppressed the growth of colon carcinoma 26 in mice by 80%, 92% and 94%, respectively, whereas free LDM at 0.1 mg/kg suppressed the growth by 77%. The survival time of tumor-bearing mice was also increased by Fab'-LDM conjugate treatment. Fab'-LDM conjugate was more effective than equivalent unconjugated LDM (P < 0.01). CONCLUSIONS: The immunoconjugate composed of LDM and Fab' fragment that is characterized by downsized-molecule shows remarkable effectiveness against tumor growth.

Aminoglycosides↗
PubMed2003

[Antitumor effects of the immunoconjugate composed of lidamycin and monoclonal antibody 3G11].

AIM: To study the antitumor effects of an immunoconjugate composed of lidamycin (LDM) and monoclonal antibody 3G11 (3G11-LDM conjugate). METHODS: 3G11-LDM conjugate was prepared by using 2-iminothiolane (2-IT) and m-maleimidobenzoyl-N-hydroxy-succimide ester (MBS) as crosslinkers. The molecular weight of the conjugate was measured on non-reduced SDS-PAGE gel. Immunoreactivity of 3G11-LDM conjugate to type IV collagenase or to hepatoma 22 cells was determined by ELISA. The cytotoxicity of the immunoconjugate to hepatoma 22 cells was examined by MTT assay. Antitumor effects of the 3G11-LDM conjugate in vivo were evaluated using subcutaneously transplanted hepatoma 22 tumor model in mice. RESULTS: The molecular weight of 3G11-LDM conjugate was approximately 160 kDa. 3G11-LDM conjugate retained part of the immunoreactivity of 3G11 to type IV collagenase and hepatoma 22 cells. As compared with free LDM, 3G11-LDM conjugate showed stronger cytotoxicity to hepatoma 22 cells. When administered intravenously (i.v. x 2 on day 1 and 8), 3G11-LDM conjugate, at doses of 0.05 and 0.10 mg.kg-1, inhibited the growth of hepatoma 22 in mice by 87.8% and 97.2% on day 11, respectively, whereas the unconjugated LDM at 0.05 mg.kg-1 inhibited tumor growth by 67.1%. The median survival times for tumor-bearing mice of untreated control, LDM at 0.05 mg.kg-1, 3G11-LDM at 0.05 mg.kg-1, and 3G11-LDM at 0.10 mg.kg-1 were 34, 41.5, 60.5 and 94 d, respectively. Evidently 3G11-LDM was more effective than free LDM in suppressing tumor growth and prolonging the life span of tumor-bearing mice. CONCLUSION: 3G11-LDM conjugate shows much stronger antitumor effects than equivalent dose of free LDM and may have promising therapeutic potential in cancer treatment.

Aminoglycosides↗
PubMed2005

[Killing effect of Photofrin-Herceptin immunoconjugate on tumor cell lines in vitro].

OBJECTIVE: To study the specific killing effect of the Photofrin-Herceptin immunoconjugate on the tumor cells expressing HER-2. METHODS: Photofrin (porfimer sodium) was covalently coupled to Herceptin (trastuzumab) via [1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide hydrochloride](EDCI) , and the killing effect of this conjugate was evaluated by means of MTT assay on SK-BR-3, MCF-7 and A549 cell lines expressing HER-2 at different levels. RESULTS: The conjugate had weaker immunoactivity than Herceptin, but possessed stronger killing effect on the cell lines expressing HER-2 than Photofrin, Herceptin, as well as the mixture of Photofrin and Herceptin (P<0.05). In the cell lines negative for HER-2 expression, the killing effect of the conjugate was similar to that of Photofrin, Herceptin, and their mixture. CONCLUSION: Photofrin-Herceptin immunoconjugate can specifically kill HER-positive cells in vitro.

Antibodies, Monoclonal↗
PubMed2006

[Antitumor effect of the novel immunoconjugate composed of pingyangmycin and anti-type IV collagenase monoclonal antibody].

AIM: To study the antitumor effect of an immunoconjugate composed of pingyangmycin (PYM) and anti-type IV collagenase monoclonal antibody (mAb) 3G11. METHODS: 3G11-PLG-PYM immunoconjugate was prepared by linking 2-iminothiolane (2-IT) modified mAb to PYM via N-succinimidyl-3-(2-pyridyldithiol) -propionate (SPDP) derived poly-alpha-L-glutamic acid (PLG) backbone as the intermediate drug carrier. Characterization of the conjugate was performed by SDS-PAGE and spectrophotometry. Immunoreactivity of the conjugate against type IV collagenase was determined by ELISA. The cytotoxicity of the conjugate to hepatoma 22 (H22) and KB cells was examined by MTT assay. Antitumor effect of the conjugate in vivo was evaluated in mice bearing subcutaneously implanted H22 tumor, the candidate drugs were administered intravenously by "q2d x 6" regimen. RESULTS: The molecular weight of the conjugate was approximately 170 kD. The molecular ratio of 3G11-PLG-PYM was 1 : 2. 4 : 10. The conjugate retained part of the immunoreactivity of mAb 3G11 against the antigen. The cytotoxicity of the conjugate to H22 and KB cells was moderate comparing with free PYM. In vivo however, free PYM inhibited the growth of H22 by 60.6% on day 22 at the dose of 10 mg x kg(-1), while the equivalent dose of 3G11-PLG-PYM conjugate reached 90.8%. The median survival time of the mice treated with the conjugate was prolonged by 71.7% as compared with that of the untreated group, whereas that of free PYM prolonged only 10.9%. 3G11-PLG-PYM conjugate was notably more effective than free PYM in tumor suppression and life span prolongation. CONCLUSION: 3G11-PLG-PYM displayed more marked antitumor efficacy than free PYM in vivo and might be a novel candidate for cancer treatment.

Animals↗
PubMed1998

In vivo toxicity and pharmacokinetic features of B43 (anti-CD19)-genistein immunoconjugate in nonhuman primates.

B43 (anti-CD19)-genistein immunoconjugate targets genistein, a naturally occurring protein tyrosine kinase-inhibitory isoflavone to the membrane-associated antiapoptotic CD19-LYN complexes and triggers apoptotic cell death. In this preclinical study, the toxicity profiles of B43-genistein as well as unconjugated genistein were evaluated in cynomolgus monkeys. B43-genistein and genistein were administered either as single bolus injections or daily injections for 5-10 consecutive days via the i.v. route to monkeys. Neither genistein nor B43-genistein was toxic to cynomolgus monkeys, and no test article-related histopathological lesions were found in any of the two genistein-treated or five B43-genistein-treated cynomolgus monkeys. B43-genistein showed a favorable pharmacokinetics in monkeys, with a plasma half-life of 10-23 h. Plasma samples from B43-genistein-treated monkeys elicited potent and CD19 antigenspecific antileukemic activity against human CD19+ leukemia cells in vitro. To our knowledge, this is the first preclinical toxicity and pharmacokinetic study of a tyrosine kinase inhibitor-containing immunoconjugate in nonhuman primates.

Animals↗
PubMed1998

Comparison of 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-peptide-ChL6, a novel immunoconjugate with catabolizable linker, to 2-iminothiolane-2-[p-(bromoacetamido)benzyl]-DOTA-ChL6 in breast cancer xenografts.

Radioimmunotherapy using 131I-ChL6 antibody has shown promise in patients with breast cancer. To enhance this potential, a novel ChL6 immunoconjugate that is catabolizable and tightly binds 90Y and (111)In was developed. The immunoconjugate, 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-peptide-ChL6, consists of the macrocyclic chelator DOTA linked to ChL6 by a peptide that is preferentially catabolized in the liver. The pharmacokinetic and dosimetric properties of the radioimmunoconjugates (RICs) (111)In- and 90Y-DOTA-peptide-ChL6 and (111)In- and 90Y-2-iminothiolane (2-IT)-2-[p-(bromoacetamido)benzyl]-DOTA-ChL6 were compared in athymic mice bearing HBT3477 human breast cancer xenografts. Each of the RICs was stable in vivo and concentrated well in the xenografts. Liver concentration, cumulative radioactivity (activity over time), and radiation dose of the DOTA-peptide-ChL6 RICs were one-third to one-half of those of the corresponding 2-IT-2-[p(bromoacetamido)benzyl]-DOTA-ChL6 RICs. Indium-111 RICs were imperfect tracers for corresponding 90Y RICs, although their pharmacokinetics and radiation dosimetries were similar. The results of this study were consistent with previously published in vitro data, which indicated that the peptide linker of DOTA-peptide-ChL6 was catabolized by cathepsin B. The cumulative activities and radiation doses to the liver of DOTA-peptide-ChL6 RICs were one-half of those of corresponding RICs with the 2-IT linker. Preliminary data from pilot studies in patients with breast cancer are in accord with these observations. These novel DOTA-peptide RICs seem to have excellent clinical potential for radioimmunotherapy associated with marrow transplantation, for which liver radiation is likely to be dose limiting for 90Y.

Animals↗
PubMed1995

Analysis of monoclonal antibody chimeric BR96-doxorubicin immunoconjugate by sodium dodecyl sulfate-capillary gel electrophoresis with ultraviolet and laser-induced fluorescence detection.

Sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CAGE), the capillary version of SDS-polyacrylamide-based slab gel electrophoresis, has been utilized for the separation and analysis of monoclonal antibody chimeric BR96 and the corresponding immunoconjugate prepared between BR96 and the anticancer drug doxorubicin (BR96-DOX). SDS-CAGE was performed in a coated capillary column filled with a polymer solution-based gel network matrix. Two detection formats, a uv absorbance detector and an argon-ion laser-based fluorescence detector, were incorporated into this system, providing complementary information for the determination of conjugated species. Both monoclonal antibody and immunoconjugates were studied in their native, denatured, and denatured and reduced states, respectively. Six peaks were identified following separation of the denatured BR96-DOX. These peaks were confirmed to correspond to all the possible conjugated species as expected. Analysis of the resulting "fingerprint" maps indicated that the light, heavy, and light-heavy chain conjugates are the predominant species. SDS-CAGE offers an alternative approach to the conventional slab gel electrophoresis and other chromatographic techniques, providing rapid, efficient, sensitive, and accurate information for the analysis of antibody and bioconjugates.

Antibodies, Monoclonal↗
PubMed1988

In vivo antitumor activity demonstrated with squamous carcinoma reactive monoclonal antibody-Vinca immunoconjugates.

An immunoconjugate (PF1/D-DAVLBHYD), made with the squamous carcinoma reactive monoclonal antibody PF1/D and a derivative of vinblastine, DAVLBHYD, was shown to suppress established T222 human tumor nude mouse xenografts using a multidose protocol. Treatments of xenograft-bearing mice with free drug, free antibody, or a mixture of the two, were unsuccessful at achieving suppression without associated toxicity, using otherwise identical protocols. A Vinca conjugate with a related squamous carcinoma reactive monoclonal antibody, PF1/B, was shown to have similar tumor suppressive activity. In a dual immunoconjugate therapy protocol, PF1/D-DAVLBHYD and PF1/B-DAVLBHYD had additive antitumor effects which were consistent with their complementary tumor reactivity.

Animals↗
PubMed1992

Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: anti-SSEA-1 and MOPC 104E in mouse teratocarcinomas and normal tissues.

Methotrexate (MTX) was coupled to the tumor-targeting monoclonal IgM, anti-SSEA-1 and the non-targeting myeloma IgM, MOPC 104E. At 24-h intervals following injection, drug deposition in MH-15 teratocarcinomas and in several normal tissues was followed by immunoperoxidase microscopy using the M16 monoclonal antibody to MTX. MTX-anti-SSEA-1 was deposited on the surface and in the interior of living tumor cells 24 h after injection; at 48 h and after, only low-level binding to necrotic tissue was found. There was no significant gradation in staining from the outside to the interior of the tumors. In tumors, the control MOPC 104E immunoconjugate was detectable only in necrotic tissue. Binding to SSEA-1-expressing normal tissues was undetectable, except for pericryptal fibroblasts in the small intestine. No significant pathology was found in normal tissues that are SSEA-1 positive. High levels of the immunoconjugate were detected in the liver, where MTX was found predominantly in Kupffer cells and possibly in hepatocytes; again, no significant morphological changes were associated with this retention. Thus tumor-associated antigens can be suitable targets for antibody-drug conjugates even when present in normal tissues and in large quantities, provided that the antigens in normal tissues are inaccessible. Moreover, deposition in viable tumor tissue can be assessed using monoclonal antibodies to methotrexate.

Animals↗
PubMed2001

Hepatic veno-occlusive disease in two patients with relapsed acute myeloid leukemia treated with anti-CD33 calicheamicin (CMA-676) immunoconjugate.

Monoclonal antibodies recognizing hematopoietic antigens are increasingly being used to target therapy directly at leukemic cells, with the aim of achieving sustained remission with little systemic toxicity. Administration of anti-CD33 calicheamicin immunoconjugate is commonly regarded as being safe, with only moderate systemic non-hematological side effects. We report on two cases of hepatic veno-occlusive disease in heavily pretreated patients presenting with relapsed acute myeloid leukemia (AML). Since significant liver toxicity prevented further specific therapy in both patients, we recommend that antibody therapy with anti-CD33 immunoconjugate should be applied with caution in patients presenting with risk factors for the development of hepatic veno-occlusive disease.

Acute Disease↗
PubMed1993

Evaluation of the systemic toxicity and pharmacokinetics of the immunoconjugate anti-B4-blocked ricin in non-human primates. Delivered by multiple bolus injections and by continuous infusion.

The systemic toxicity of an immunoconjugate of blocked ricin and the anti-CD19 monoclonal antibody, anti-B4, was studied in cynomolgus monkeys to evaluate its safety for use in humans. Anti-B4-blocked Ricin (Anti-B4-bR) is a highly cytotoxic immunoconjugate which can kill up to 5 logs of antigen positive target cells at concentrations easily achievable in blood. Subacute toxicity studies with Anti-B4-bR were performed in 20 cynomolgus monkeys and 4 rhesus monkeys, which, unlike humans, do not express the CD19 epitope recognized by the anti-B4 antibody on their B-lymphocytes. Anti-B4-bR was administered to cynomolgus monkeys by 5 daily intravenous bolus injections of 10 or 100 micrograms/kg/day, and non-conjugated blocked ricin was administered by 5 daily intravenous bolus injections of 30 micrograms/kg/day. Total doses of the conjugate of 200, 500, 1000 or 1500 micrograms/kg were also delivered to rhesus monkeys by continuous intravenous infusion over seven days. The clinical signs of toxicity, clinical pathology parameters, and gross and microscopic tissue changes associated with Anti-B4-bR were minimal to moderate where present, and primarily hepatic. In monkeys treated with 5 x 10 micrograms/kg of Anti-B4-bR, lesions were noticeable on day 7 after the start of the treatment but were less severe or absent on day 14, suggesting that the toxic effects were reversible. Clearance of the conjugate from the serum after bolus injections of Anti-B4-bR was evaluated by ELISA and demonstrated an initial t 1/2(alpha) of 1.4-2.0 h and a secondary t 1/2(beta) of about 14 h. Serum concentrations of Anti-B4-bR were about 10-20-fold lower at 24 h as compared to 1 h after each of the 5 bolus injections in monkeys. Continuous infusion of Anti-B4-bR in primates achieved plateau levels of the immunotoxin in blood for almost the entire duration of the infusion. The therapeutic utility of the Anti-B4-bR is currently being evaluated in patients with B-cell malignancies.

Animals↗
PubMed1989

Doxorubicin-anti-carcinoembryonic antigen immunoconjugate activity in vitro.

An in vitro model consisting of a series of 11 human cancer cell lines with varying density of expression of membrane carcinoembryonic antigen (CEA) has been used to evaluate conjugates of doxorubicin (Adriamycin) covalently linked by a carbodiimide method to goat polyclonal antibodies and mouse monoclonal antibodies to CEA. Conjugates were produced which retained both antigen binding and drug cytotoxicity. IC50 values were determined for free drug, free drug mixed with unconjugated antibodies and for the immunoconjugates. Cell lines that were very sensitive to free drug (IC50 less than 100 ng/ml) were also found to be highly sensitive to conjugated drug and similarly cell lines resistant to drug (IC50 greater than 1,000 ng/ml) were also resistant to conjugated drug. Although there was no correlation between CEA expression and conjugates efficacy, competitive inhibition studies using autologous antibody to block conjugate binding to cells indicated immunoconjugates specificity for the CEA target.

Antibodies↗
PubMed1993

Antitumour activity of an immunoconjugate composed of anti-human astrocytoma monoclonal antibody and neocarzinostatin.

Neocarzinostatin (NCS) linked to the thiol group on the hinge region of the Fab' fragment of GA-17, a murine monoclonal antibody reacting with tyrosine-specific phosphorylated antigens, which are exclusively expressed on the cell surface of human astrocytomas, was evaluated for in vivo activity. GA-17-NCS immunoconjugates significantly suppressed the growth of human malignant glioma cell line U87-MG subcutaneous xenografts in nude mice until day 50 when administered intravenously into the tail vein. Disulphide- and thioether-linked GA-17-NCS were nearly equipotent immunoconjugates, but thioether-linked GA-17-NCS was more effective than disulphide-linked conjugates with 250 U/kg NCS content on day 50 (P < 0.05). Thioether-linked GA-17-NCS was significantly more effective on day 50 than free NCS with 500 U/kg or 250 U/kg NCS content (P < 0.05, P < 0.01, respectively). These results suggest that GA-17-NCS may prove useful in the treatment of human malignant gliomas.

Animals↗
PubMed1995

Novel doxorubicin-monoclonal anti-carcinoembryonic antigen antibody immunoconjugate activity in vitro.

Doxorubicin was modified with five different heterobifunctional reagents to produce drug analogs containing 3'-N-amide or C-13 hydrazone linkage with maleimide. Synthesis and characterization of two new reagents, 4-maleimidobenzohydrazide trifluoroacetate salt (13) and N-(4-maleimidobenzoyl)-6-aminocaprohydrazide trifluoroacetate salt (14) are described here. All Dox maleimido derivatives were conjugated to thiolated anti-carcinoembryonic antigen monoclonal antibody, 11-285-14, via a Michael addition reaction. Antibody-directed cytotoxicity was demonstrated with the MTT assay using combinations of antigen-positive and antigen-negative cell lines. The immunoconjugates prepared from Dox 3'-N-amide analogs are not active in vitro, however, Dox(hydrazone-linked) immunoconjugates are selectively toxic to the CEA positive cell line.

Adenocarcinoma↗
PubMed2000

Synthesis of a novel duocarmycin derivative DU-257 and its application to immunoconjugate using poly(ethylene glycol)-dipeptidyl linker capable of tumor specific activation.

Novel anti-tumor agent, duocarmycin derivative DU-257, was designed and synthesized to prepare immunoconjugate in order to confirm the feasibility of enzymatically cleavable linker consisting of poly(ethylene glycol) (PEG) and dipeptide, L-alanyl-L-valine. Oxyethylamine arm was introduced at 4-methoxy position of segment B of DU-86 to form DU-257 and evaluated its property. DU-257 retained similar stability and potency with DU-86 while enhanced hydrophilicity suggested. DU-257 was condensed to the PEG-dipeptidyl linker through carboxyl terminal of dipeptide, and enzymatic release of DU-257 using a model enzyme, thermolysin, similar enzyme of which was shown to be overexpressed at various tumor sites, was evaluated by HPLC analysis. Cleavage between the linker amino acids by the model protease and release of DU-257 as valine conjugated form was confirmed. The enzymatically released form of DU-257 expressed its cytotoxicity without loss of the potency for HeLaS3 and SW1116 tumor cell lines, although the efficacy was different in individual cells. DU-257 was then conjugated through the linker to KM231 monoclonal antibody specifically reactive to GD3 antigen which was shown to be expressed on the surface of many malignant tumors such as SW1116. The conjugate retained its binding specificity for SW1116 cell with a similar activity with KM231. Furthermore, the conjugate showed significant growth inhibition on SW1116 cell at a concentration of 75 microg/mL while no effect on antigen negative cell, HeLaS3. These results suggest that the conjugate retained its anti-tumor effect only when it bound on and was activated at the target cell, simultaneously. DU-257 will be one of the candidate of anti-tumor agent for application to immunoconjugate and its conjugate with KM231 via PEG-dipeptidyl linker will be a useful entity for cancer therapy related to sLe(a) expression.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Preparation and characterization of immunoconjugates for antibody-targeted photolysis.

Monoclonal antibody (MAb)-dextran-tin(IV) chlorin e6 (SnCe6) immunoconjugates were prepared by a new technique involving the use of reducing, terminal-modified dextran carriers and site-specific modification of the Fc oligosaccharide moiety on the antibodies. Dextran carriers were synthesized to increase the number of SnCe6 molecules attached to a MAb. The dextran carriers were coupled to the MAb via a single, chain-terminal hydrazide group to prevent aggregation of MAbs. Conjugates were prepared with antimelanoma MAb 2.1 containing up to 18.9 SnCe6 molecules per MAb. Under neutral conditions, no hydrolysis of the hydrazone bond between the MAb and the dextran carrier could be detected, and the hydrazone was not stabilized by reduction with NaCNBH3 or NaBH4. Analysis of the purified immunoconjugates showed that approximately two dextran carrier chains were attached to a MAb regardless of the number of SnCe6 molecules linked to a dextran carrier. Site-specific covalent attachment of the SnCe6-dextran chains to the MAb was confirmed by SDS-PAGE. HPLC analysis of the conjugates gave a single species eluting in the range of 200-240 kDa. As determined by a competitive inhibition radioimmunoassay using viable SK-MEL-2 human malignant melanoma cells, the conjugates showed excellent retention of antigen-binding activity relative to unconjugated MAb.

Antibodies, Monoclonal↗
PubMedDate not supplied

In vivo antitumor activity of a panel of four monoclonal antibody-vinca alkaloid immunoconjugates which bind to three distinct epitopes of carcinoembryonic antigen.

A panel of four murine monoclonal antibodies apparently directed against three distinct epitopes of carcinoembryonic antigen (CEA) was conjugated via oxidized carbohydrate groups to 4-desacetylvinblastine-3-carboxyhydrazide. The resulting antibody-vinca conjugates were evaluated for antitumor activity against 2-9-day-established LS174T human colorectal carcinoma xenografts. The antibodies (immunoglobulin G, IgG) employed in this study were 11.285.14 (IgG1), 14.95.55 (IgG2a), CEM231 (IgG1), ZCE025 (IgG1). Additive immunofluorescence studies indicated that CEM231 and ZCE025 recognized the same or a closely related epitope(s) on CEA which was distinct from the two epitopes bound by 11.285.14 and 14.95.55. The in vivo antitumor efficacy studies demonstrated that chemoimmunoconjugates prepared from 14.95.55 and ZCE025 were more active than the conjugates constructed from the 11.285.14 and CEM231 antibodies. The 14.95.55 and ZCE025 immunoconjugates were also more efficacious than free drug or drug conjugated to irrelevant murine IgG. The presence of increased carbohydrate content on the light chain of ZCE025 may have been responsible for the ability to construct ZCE025-vinca conjugates with about twice the drug content (approximately 10 mol of vinca/mol of IgG) than was achieved with the other antibodies. The highly conjugated form of ZCE025 demonstrated similar efficacy but was much less toxic than a ZCE025 conjugate containing 5 mol of vinca/mol of IgG. These data indicated that significant differences existed in the ability of monoclonal antibodies to target a cytotoxic agent for effective antitumor activity even when the immunoconjugates recognized the same antigen or even the same or closely related antigen epitope(s). Furthermore, these differences could not have been identified without extensive in vivo evaluation for antitumor efficacy.

Animals↗
PubMed1987

Immunoconjugates: applications in targeted drug delivery for cancer therapy.

Monoclonal antibodies can be produced against virtually any molecule, and unlike polyclonal antisera, they are highly specific. There has been great improvement in the monoclonal antibody production technique since its inception in 1975. The idea behind using monoclonals to direct cancer treatments is based on the fact that surfaces of tumor contain a wide variety of proteins, some of which are specific to the tumor type. Monoclonal antibodies that bind to such tumor-specific antigens could be used, either alone or as conjugates of drugs and toxins (immunoconjugates), to selectively seek out and destroy these tumor cells. Targeted drug delivery therapy of tumor using monoclonals or their conjugates has been reported by many investigators, and the early results are quite promising. However, many obstacles still have to be overcome before immunoconjugates become a valuable agent in the treatment of human diseases including cancer.

Adjuvants, Immunologic↗