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Hybridoma Apr 1995The immune status of ovarian cancer patients receiving anti-CA125 murine monoclonal antibody B43.13 was evaluated by measuring antiidiotypic antibodies (Ab2),...
Antiidiotype induction therapy: evidence for the induction of immune response through the idiotype network in patients with ovarian cancer after administration of anti-CA125 murine monoclonal antibody B43.13.
The immune status of ovarian cancer patients receiving anti-CA125 murine monoclonal antibody B43.13 was evaluated by measuring antiidiotypic antibodies (Ab2), antiantiidiotypic antibodies (Ab3), antiisotypic human antimouse antibodies (HAMA), interferon-gamma, and CA125 levels in the serum. A specific assay was developed for the determination of Ab2 antibodies using chimeric MAb B43.13. Of the 50 patients studied, 26 had elevated levels of Ab2. Eleven of these 26 patients also had high titer of antiantiidiotypic (Ab3) antibodies. Eight of the 22 patients analyzed had increased interferon-gamma levels. A tentative correlation was found between survival of these patients' antiidiotype induction.
Topics: Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; CA-125 Antigen; Female; Humans; Ovarian Neoplasms; Retrospective Studies
PubMed: 7590780
DOI: 10.1089/hyb.1995.14.199 -
Tumour Biology : the Journal of the... 1996We evaluated the immunohistological (IH) characteristics of 22 different antibodies that were submitted for study in the frame of the TD-1 ISOBM Workshop on monoclonal...
We evaluated the immunohistological (IH) characteristics of 22 different antibodies that were submitted for study in the frame of the TD-1 ISOBM Workshop on monoclonal antibodies against CA125. Information on relative affinities and epitope similarities was obtained from a parallel immunochemical study. Antibodies were tested at concentrations of 10 and 1 micrograms/ml on frozen and paraffin sections. Paraffin sections were stained according to the streptavidin-biotin complex protocol, and frozen sections according to a two-step immunoperoxidase technique. Aminoethylcarbazole served as the chromogen. The tissues were from normal proliferative endometrium (formalin-fixed paraffin-embedded) material and clear-cell adenocarcinoma of the ovary (formalin-fixed paraffin-embedded and frozen material). Sections were scored for staining in epithelial cells, basal, apical and diffuse cytoplasmic and in stromal components. Intensity was graded as 1, 2 or 3 for epithelial cells and as -1, -2 or -3 for stroma. The cumulative scores for each antibody expressed the discriminative properties of specific epithelial staining against background. M11 and M11-like antibodies, as well as OC125 and OC125-like antibodies, in general showed good staining results. Although there was a trend for high-affinity antibodies to show higher scores, there was no clear relationship between affinity and staining result. For nine antibodies (ZR45, MA602-1, K102, K94, K90, OV185, K97, K96, OV198), the reactions in paraffin and frozen sections were of similar intensity. Most of these were of low affinity with one exception: antibody ZR45, a rat monoclonal antibody (MAb) which had a high relative affinity. For eight antibodies (M11, K101, MA602-6, ZS33, B27.1, B43.13, K93, OC125), a loss of specific staining was observed in frozen sections. All but two of these antibodies (MA602-6 and OC125) were of high relative affinity. With four antibodies (K91, ZR38, K95, K100), the reverse situation was observed. One (K100) was of low affinity, two (K95 and K91) of high affinity and the fourth (ZR38) was a rat MAb of high affinity. Mainly due to the increased cytoplasmic staining in carcinoma, the reactivity in paraffin sections was less extensive in normal endometrium compared to ovarian carcinoma for the majority of antibodies, irrespective of their affinity or epitope group. The IH characterization of these antibodies may be of help in selecting antibodies with specific properties for further comparative studies. The reactivity of normal endometrium with all useful antibodies makes it a good candidate for standard external IH tissue control.
Topics: Adenocarcinoma, Clear Cell; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antibody Specificity; CA-125 Antigen; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Ovarian Neoplasms; Paraffin Embedding; Rats; Tissue Fixation
PubMed: 8938947
DOI: No ID Found -
APMIS : Acta Pathologica,... Jan 2013To evaluate if heterogeneity of tissue cancer antigen 125 (CA125) expression is present in epithelial serous adenocarcinomas. Furthermore, to investigate whether there...
To evaluate if heterogeneity of tissue cancer antigen 125 (CA125) expression is present in epithelial serous adenocarcinomas. Furthermore, to investigate whether there is a correlation between levels of CA125 tissue expression, serum level of CA125, stage, and grade. A total of 10 patients diagnosed with serous ovarian adenocarcinomas were included. Preoperative blood samples were collected to determine serum CA125 levels. Tumor tissue from primary surgery was collected and processed for immunohistochemical analyses. CA125 was expressed in varying degrees in tumor tissues from all patients. Mean tissue CA125 expression for each patient ranged from 36% to 98%. Intrapatient variations in tissue expression ranged from 10% to 90% point. No significant correlations between levels of CA125 tissue expression, serum level of CA125, stage, and grade were found. We found that the tissue expression of CA125 is heterogenic. Although most patients had a high mean expression, it covers a large intrapatient variation in expression. This suggests that if using CA125 as a tissue marker and anti-CA125 (oregovomab) as immunotherapy treatment in future studies, it will be necessary to take heterogeneity into consideration and examine a larger number of biopsies. Therefore, the study demonstrates the need for heterogeneity studies in future translational research.
Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; CA-125 Antigen; Female; Humans; Immunohistochemistry; Middle Aged; Ovarian Neoplasms; Statistics, Nonparametric; Tissue Array Analysis
PubMed: 23030299
DOI: 10.1111/j.1600-0463.2012.02943.x -
Cancer Biotherapy & Radiopharmaceuticals Jun 2001The murine monoclonal anti-CA125 antibody MAb-B43.13 has previously been administered as an immunoscintigraphic agent in order to monitor recurrence of ovarian cancer in...
Induction of CA125-specific B and T cell responses in patients injected with MAb-B43.13--evidence for antibody-mediated antigen-processing and presentation of CA125 in vivo.
The murine monoclonal anti-CA125 antibody MAb-B43.13 has previously been administered as an immunoscintigraphic agent in order to monitor recurrence of ovarian cancer in patients, and a long-term follow-up demonstrated a survival benefit for these patients. The clinical benefit was initially attributed to the activation of the idiotypic network. The objective of this study was to investigate the role of CA125-MAb-B43.13 immune complex formation on the induction of CA125-specific immune responses. Analysis of patient serum samples from pharmacokinetic studies demonstrated that the antibody forms immune complexes with CA125 in circulation within 30 minutes of injection. Induction of humoral and cellular anti-CA125 responses correlated with the amount of circulating CA125 antigen present at time of antibody injection. Subsequent to the injection of MAb-B43.13, the patients generated anti-CA125 antibodies that were directed against various epitopes on the antigen and were not restricted to the specific epitope recognized by MAb-B43.13. The generation of CA125-specific B and T cell responses after MAb-B43.13 injection correlated with improved survival. The influence of circulating CA125 for the induction of CA125-specific immune responses and the multi-epitopic nature of the human anti-CA125 antibodies suggest that the majority of these antibodies were not induced via the idiotypic network but by the autologous antigen itself. Since antibody and T cell responses to CA125 were not present before injection of MAb-B43.13, it is hypothesized that complex formation of MAb-B43.13 with circulating antigen triggers the induction of CA125-specific immune responses.
Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antibody-Dependent Cell Cytotoxicity; Antigen Presentation; Antigen-Antibody Complex; Antigens, CD; B-Lymphocytes; CA-125 Antigen; Female; Histocompatibility Antigens Class II; Humans; Injections, Intravenous; Lymphocyte Activation; Middle Aged; Neoplasm Metastasis; Ovarian Neoplasms; Survival Rate; T-Lymphocytes; Tumor Cells, Cultured
PubMed: 11471484
DOI: 10.1089/10849780152389384 -
Clinical Advances in Hematology &... Nov 2005
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; CA-125 Antigen; Dioxoles; Erlotinib Hydrochloride; Female; Humans; Isoquinolines; Ovarian Neoplasms; Predictive Value of Tests; Quinazolines; Recurrence; Remission Induction; Survival Rate; Tetrahydroisoquinolines; Trabectedin; Vascular Endothelial Growth Factor A
PubMed: 16491624
DOI: No ID Found -
Journal of Pharmacy & Pharmaceutical... 1998PURPOSE. This article reports the pharmacokinetics, radiation dosimetry and radioimmunoscintigraphy (RIS) of two (99m)Tc-labelled monoclonal antibodies (MAb) used to... (Clinical Trial)
Clinical Trial
UNLABELLED
PURPOSE. This article reports the pharmacokinetics, radiation dosimetry and radioimmunoscintigraphy (RIS) of two (99m)Tc-labelled monoclonal antibodies (MAb) used to detect cancer.
METHODS
The effects of circulating antigen in female cancer patients are explored and their effects on the ability of these MAbs to effectively perform as RIS agents noted. To illustrate the effects of circulating antigen, data using MAb B43.13 (OVAREX, AltaRex Corp., Waltham, MA, USA) from a Pilot study in ovarian cancer patients are presented. The results from a Phase II study of MAb 170H.82 (Tru-Scint AD, BIOMIRA INC., Edmonton, Alberta, Canada) in patients with primary and locally recurrent breast cancer were used to portray the biodistribution patterns when no circulating antigen is present. Data from planar gamma camera images were obtained for both groups and used for pharmacokinetic and radiation dosimetry analyses.
RESULTS
A pharmacokinetic analysis indicated a shorter residence time and higher clearance of (99m)Tc-MAb-B43.13 that was ascribed in part to the circulating CA 125 antigen in this group of ovarian cancer patients.
CONCLUSION
These clearance patterns resulted in acceptable, though higher radiation doses to the spleen and urinary bladder wall for these patients when compared to the MAb-170H.82 group. Both MAbs were found to produce acceptable radioimmunoscintigraphic images
Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Breast Neoplasms; CA-125 Antigen; Female; Humans; Image Processing, Computer-Assisted; Middle Aged; Organotechnetium Compounds; Ovarian Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution
PubMed: 10948399
DOI: No ID Found -
Hybridoma Feb 1999The monoclonal antibody (MAb) B43.13, binding to the ovarian cancer-associated antigen CA125, has been injected into more than 200 patients with ovarian cancer to detect...
The monoclonal antibody (MAb) B43.13, binding to the ovarian cancer-associated antigen CA125, has been injected into more than 200 patients with ovarian cancer to detect recurrence of the disease. The follow-up of the patients revealed surprisingly long survival spans for several patients despite high CA125 levels. To investigate the therapeutic effectiveness of OvaRex MAb-B43.13 (AltaRex, Edmonton, Canada) under well-controlled conditions, the antibody was tested in a human-PBL-SCID/BG mouse model with CA125 positive human ovarian cancer cells. Mice were reconstituted with human peripheral blood lymphocytes (PBL, normal donors) by intraperitoneal (IP) injection of 2 to 3 x 10(7) PBL/mouse. OvaRex MAb-B43.13 was administered at 100 microg/mouse in phosphate buffered saline (PBS), in three different experimental set-ups. An isotype-matched control antibody (MOPC21 or MAb-170) and PBS injection served as controls. The ovarian cancer cell line NIH:OVCAR-NU-3 was injected IP at 1 x 10(6) cells/mouse or subcutaneously (SC) at 4 x 10(6) cells/mouse. Human-PBL-SCID/BG mice were either immunized before injection of tumor cells, along with tumor cells or after small tumors were established (2 weeks after transplantation). Antibody injections were repeated twice in 2-week intervals. Functional and cellular characterization of serum and PBL from these mice demonstrated the successful engraftment of a human immune system in those mice. All three experiments showed that OvaRex MAb-B43.13 treatment could (a) delay or prevent development of tumors; (b) reduce the size of small established tumors (SC tumor injection) or suppress ascites formation; (c) delay tumor growth when injected prior to tumor implantation; and (d) prolong the survival of the mice (i.p. tumor injection).
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; CA-125 Antigen; Disease Models, Animal; Female; Flow Cytometry; Humans; Immunoglobulin G; Immunohistochemistry; Immunotherapy; Mice; Mice, SCID; Ovarian Neoplasms; Tumor Cells, Cultured
PubMed: 10211788
DOI: 10.1089/hyb.1999.18.47 -
Cancer Immunology, Immunotherapy : CII Sep 1998The use of biodegradable poly(DL-lactic-co-glycolic acid) microspheres as a cancer vaccine delivery system for induction of anti-idiotypic responses was investigated...
Induction of anti-idiotypic humoral and cellular immune responses by a murine monoclonal antibody recognizing the ovarian carcinoma antigen CA125 encapsulated in biodegradable microspheres.
The use of biodegradable poly(DL-lactic-co-glycolic acid) microspheres as a cancer vaccine delivery system for induction of anti-idiotypic responses was investigated using a murine monoclonal antibody B43.13 that recognizes the human ovarian cancer antigen CA125. Immunization of mice with mAb B43.13 encapsulated in poly(DL-lactic-co-glycolic acid) microspheres resulted in enhanced humoral and cellular immune responses compared with mAb B43.13 alone or mAb B43.13 mixed with microspheres. The antibody responses could be further enhanced by the co-encapsulation of mAb B43.13 with monophosphoryl lipid A, a non-toxic adjuvant, in microspheres. Anti-idiotypic humoral responses were shown to result in Ab2 antibodies mimicking the nominal antigen CA125 and Ab3 antibodies recognizing CA125. Further, microsphere delivery of mAb B43.13 also resulted in induction of T cell responses involving T2 cells reactive with mAb B43.13 epitopes and T3 cells recognizing CA125. These results indicate that microsphere delivery of Abl can induce both humoral and cellular anti-idiotypic responses relevant to cancer antigens. This raises the possibility of the use of such formulations for anti-idiotypic induction immunotherapy for cancer.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antibody Formation; Biocompatible Materials; CA-125 Antigen; Female; Humans; Immunity, Cellular; Lactic Acid; Mice; Mice, Inbred BALB C; Microspheres; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; T-Lymphocytes
PubMed: 9755874
DOI: 10.1007/s002620050499 -
PloS One 2018Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer.
METHODS
Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted.
RESULTS
Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64-0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53-0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73-1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95).
CONCLUSION
Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers?
Topics: Adjuvants, Pharmaceutic; Antineoplastic Agents; Aspirin; Decision Making; Evidence-Based Medicine; Humans; Neoplasms; Observational Studies as Topic; Treatment Outcome
PubMed: 30252883
DOI: 10.1371/journal.pone.0203957