Biomedical subjects

L F Massuger

Publications and source records attributed to L F Massuger.

42 records · Page 3Linked to original sources

PubMed1988

Clinical applications of monoclonal antibodies against ovarian cancer-associated antigens.

Monoclonal antibodies (McAbs), reactive with tumour-associated antigens (TAAs) present on tumour cells, appear to offer new possibilities in the diagnosis and treatment of cancer (Table I). In addition to these prospects for clinical application, monoclonal antibodies also serve as useful instruments in basic cancer research. The hybridoma technology initiated by Köhler and Milstein in 1975, underwent a very rapid development and has now shown its potential in the field of oncology. This technique made it possible to produce very large quantities of homogeneous antibodies of a stable quality. These McAbs often recognize only one antigenic determinant, or epitope, of cell surface and other molecules. This high specificity is essential for in vivo applications, especially in therapeutic immunotargeting. A central question is whether the antibodies can reach and identify those antigens on ovarian tumour cells that are not shared with normal tissues. Various antibodies have been described in the field of gynaecological oncology, which are assumed to be capable of recognizing such ovarian tumour-related antigens. These McAbs, single or in combination, are capable of showing, unambiguously, the presence of various tumour-associated antigens on ovarian carcinoma cells either in tissue or, when antigen shedding occurs, in blood. However, these McAbs may also react with tumour-associated antigens present on endometrial, cervical, colorectal, breast or other carcinoma cells. The original immunogens used to generate these McAbs differ as to their origin: ovarian cancer cells, breast cancer cells, human milk-fat preparations, trophoblastic cells, endometrial cancer cells have been used as well as osteogenic sarcoma cells, epidermoid carcinoma cells and small-cell lung cancer, colorectal, pancreatic and laryngeal carcinoma cells. The histological distribution patterns of the antigens recognized by these McAbs vary widely: cross-reactions with normal tissue and with carcinomas different from those used as immunogen are frequently seen.

Antibodies, Monoclonal↗

PubMedDate not supplied

Intraperitoneal radioimmunotherapy in an ovarian carcinoma mouse model: Effect of the radionuclide.

Despite debulking surgery and multidrug chemotherapy, advanced stage ovarian cancer has a high mortality rate. Radioimmunotherapy (RIT) is a treatment modality using specific, radiolabeled antibodies that guide cytotoxic radionuclides to cancer cells. In the present study, the therapeutic efficacy of RIT with murine monoclonal antibody HMFG1 labeled with three different beta-radiation emitting radionuclides (90Yttrium, 186Rhenium, and 131Iodine) was assessed in athymic BALB/c mice with intraperitoneally growing NIH:OVCAR-3 ovarian carcinoma xenografts. Each of the three intraperitoneally administered radiolabeled antibody preparations (90Y-HMFG1, 186Re-HMFG1, and 131I-HMFG1) caused a significant delay in ascites formation and mortality as compared to the control groups treated with 90Y-labeled irrelevant antibody, nonradiolabeled HMFG1, or phosphate buffered saline. Intraperitoneally (ip) administered 90Y-HMFG1 was shown to have a significantly higher abdominal retention as compared to the intraperitoneally administered irrelevant antibody 90Y-G250. Furthermore, intraperitoneally administered 90Y-HMFG1 more effectively inhibited tumor growth than intravenously administered 90Y-HMFG1. It was concluded that in intraperitoneally located malignant disease with ascitic cell clusters and tumor deposits, intraperitoneal administration of RIT seemed preferable as compared to intravenous administration. The choice of the most optimal radionuclide in intraperitoneally located malignancies needs further research, but could well depend on tumor characteristics such as the size of the tumor lesions.

Animals↗

PubMedDate not supplied

Normal appearing endometrial cells in cervical smears of asymptomatic postmenopausal women have predictive value for significant endometrial pathology.

The objective of this study was to determine whether postmenopausal asymptomatic women with normal endometrial cells in their smear are at higher risk for endometrial pathology compared with women without these cells. Histologic follow-up outcome and otherwise cytologic follow-up of 29,144 asymptomatic postmenopausal women was determined. Presence of normal endometrial cells, age, use of hormones, and reported elevated maturation index were assessed. The effect of each variable on outcome as well as the combined effect were evaluated. Prevalence rate of (pre)malignant uterine disease was significantly higher when normal endometrial cells were found in the cervical smear (6.5%) as compared to smears without these cells (0.2%), resulting in a relative risk of 40.2 (95% CI 9.4-172.2). Neither age nor hormone use or elevated maturation index showed significant impact on the outcome. Asymptomatic postmenopausal women with normal endometrial cells in their smear are at significant higher risk for (pre)cancerous endometrial lesion than women without these cells. These cases should be reported to the physician with an explicit comment that normal endometrial cells in a smear of a postmenopausal woman is an abnormal finding, possibly associated with significant endometrial pathology. It raises the question whether further gynecological examination would be more appropriate.

Adult↗

PubMedDate not supplied

Biodistribution of iodine-125 and indium-111 labeled OV-TL 3 intact antibodies and F(ab')2 fragments in tumor-bearing athymic mice.

The monoclonal antibody OV-TL 3, directed against an ovarian carcinoma-associated antigenic determinant, was tested as a vehicle for radioimmunolocalization of ovarian carcinomas in athymic mice bearing NIH:OVCAR-3 xenografts. The biodistribution of intact. OV-TL 3 was compared with the distribution of OC 125. Tumor uptake with OV-TL 3 was significantly higher than with OC 125, and almost 7 times higher than with a non-specific control antibody (OV-TL 19). Administration of a mixture of intact OV-TL 3 and OC 125 did not improve tumor uptake in comparison with OV-TL 3 alone. Subsequently, intact OV-TL 3 and its F(ab')2 fragments were labeled with either 111In or 125I. The highest tumor uptake was obtained with 111In-labeled intact OV-TL 3 (14.7% ID/g, 48 hr p.i.). For both antibody forms uptake of 111In in liver, spleen and kidneys was very high. Furthermore, 111In cleared more slowly from most tissues than 125I. As a result, tumor/tissue ratios with 111In-labeled OV-TL 3 were lower than with 125I-labeled OV-TL 3. The highest tumor/tissue ratios (6.9 to 53) were obtained with 125I-labeled OV-TL 3 F(ab')2 fragments, 48 hr post injection. 111In-labeled OV-TL 3 F(ab')2 has already been shown to be a clinically useful label for the detection of ovarian cancer. The results of our comparative animal study suggest that these clinical results may even be improved by using 123I-labeled OV-TL 3 F(ab')2.

Animals↗

PubMedDate not supplied

Tumour targeting of the anti-ovarian carcinoma x anti-CD3/TCR bispesific monoclonal antibody OC/TR and its parental MOv18 antibody in experimental ovarian cancer.

The anti-tumour x anti-T-cell bispecific monoclonal antibody (biMAb) OC/TR is a biologically produced biMAb combining the anti-ovarian carcinoma activity of the MOv18 MAb with anti-CD3/T-cell receptor (TCR) complex activity. In this study, the in vitro binding characteristics of the OC/TR biMAb and its tumour targeting potential in nude mice with Hela tumours was studied. Scatchard analysis revealed that the affinity constant of the biMAb was 7 times lower than the affinity of the parental MOv18 antibody. Uptake of the OC/TR antibody in the Hela xenografts in nude mice was significantly higher than the tumour uptake of an irrelevant control antibody, indicating that the radioiodinated OC/TR biMAb specifically localized in the tumour xenografts. However, tumour uptake was significantly lower than the tumour uptake of the parental MOv18 antibody. This reduced tumour uptake most likely is a result of its reduced affinity. We conclude that, despite the loss of bivalent tumour cell binding, the biMAb OC/TR can still specifically localize in tumours. This indicates that the first prerequisite of an effective therapeutic approach using systemically applied biMAb can be met. Whether the interaction with human T-cells will affect the tumour targeting potential of the biMAb in patients remains to be investigated.

Animals↗

PubMedDate not supplied

Serum CA 125 measurements to identify patients with endometrial cancer who require lymphadenectomy.

BACKGROUND: Most studies evaluating the role of serum CA 125 measurements in endometrial cancer report a positive correlation with prognostic factors. The present study investigates the role of serum CA 125 measurements as a preoperative aid in the decision whether lymphadenectomy or sampling should be part of the surgical procedure. PATIENTS AND METHODS: We retrospectively studied clinical data of 98 patients with endometrial cancer (FIGO stage I to III), who had serum samples available for analysis of IMx CA 125. Clinical information was included in the analysis in the order in which it became available to the clinician. Patients were grouped retrospectively on the basis of histopathologically determined factors. Those with grade 3 tumors, and/or myometrial invasion > or = 1/2, and/or cervical involvement, and/or parametrial or adnexal tissue involvement, and/or blood vessel invasion, were retrospectively assigned to require lymphadenectomy or sampling (N = 60). All other patients were classified as not requiring such a procedure (N = 38). RESULTS: Serum IMx CA 125 concentrations correlated with all factors included in the surgical FIG0 classification. The sensitivity to identify patients who would have required a lymphadenectomy or sampling on the basis of precurretage serum CA 125 measurements ranged between 17% (10/60) with cut-off of 35 U/ml, and 53% (32/60) with a 15 U/ml cut-off. Corresponding specificity to exclude patients for lymphadenectomy or sampling ranged from 95% (36/28) to 76% (29/38), respectively. After curettage, information regarding histological grade became available. Using only this information, 17 out of 60 patients who would have required a lymphadenectomy or sampling could be identified because of their grade 3 tumor. The combination of serum CA 125 and histological grade could identify between 37% (22/60) and 65% (39/60) of the patients who required a lymphadenectomy or sampling cut-offs again ranging from 35 to 15 U/ml. CONCLUSIONS: CA 125 serum levels may provide additional information in the preoperative assessment of endometrial cancer patients. More studies are needed to establish the appropriate cut-off level for serum CA 125 in this respect.

Adult↗