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Biomedical subjects

D D Bigner

Publications and source records attributed to D D Bigner.

At least 91 records · Page 5Linked to original sources
PubMed1996

Treatment of patients with pineoblastoma with high dose cyclophosphamide.

The outcome for patients with pineoblastoma has historically been very poor, with most patients dying of disseminated disease despite irradiation. Furthermore, the low incidence of this tumor has hindered progress toward defining better treatment strategies. Here we report the activity and toxicity of cyclophosphamide administered as a single agent at a dose schedule of 2 g/m2/day for 2 successive days at monthly intervals for a maximum of four courses. Eight patients were evaluated, six newly diagnosed and two recurrent. Amongst the six newly diagnosed patients, there were three patients demonstrating partial responses, and three had stable disease throughout the cyclophosphamide treatment period. All six patients are alive and disease free after further therapy. One patient with recurrent disease demonstrated tumor progression on cyclophosphamide, and the other had stable disease throughout the cyclophosphamide treatment period. Both patients subsequently died of progressive disease. The major toxicity of high dose cyclophosphamide was hematopoietic, with one patient requiring a dose reduction after three courses due to prolonged thrombocytopenia. One patient was also withdrawn from treatment with cyclophosphamide due to impaired pulmonary function. This study demonstrates the activity of high dose cyclophosphamide in the treatment of pineoblastoma and may serve as basis for the design of future studies of this tumor.

Adolescent↗
PubMed1996

Successful treatment of childhood pilocytic astrocytomas metastatic to the leptomeninges with high-dose cyclophosphamide.

Leptomeningeal dissemination of childhood pilocytic astrocytoma (PA) is a rare event with little information available regarding therapy. We report here four children with disseminated PA whom we treated with high doses of cyclophosphamide with clinical benefit. The patients were aged 2.5 to 8 years. Three patients presented with PA localized in the posterior fossa, initially treated with surgical resection (n = 3) and radiotherapy (n = 1). Leptomeningeal dissemination occurred at 32, 44, and 8 months from diagnosis, respectively. The fourth patient presented with an optic pathway tumor with leptomeningeal dissemination at diagnosis. At commencement of cyclophosphamide therapy, disease was present in the subarachnoid space (intracranial, n = 2; spinal, n = 4), cerebral ventricles (n = 2), and primary site (n = 3). Histology was identical at diagnosis and recurrence in the two biopsied cases and cerebrospinal fluid was negative in all cases. Treatment was with cyclophosphamide 4-5 g/m2/cycle given every 4 weeks for a total of two cycles (n = 1) and four cycles (n = 3). One patient achieved disease stabilization (duration 27 months at the time of publication) and three patients experienced significant reductions in tumor burden. Subsequent intrathecal therapy was administered to two patients. Two patients developed disease progression at 10 and 9 months from cessation of chemotherapy. The one re-treated patient responded to further, lower dose, cyclophosphamide. This is the first report of the use of high dose cyclophosphamide for disseminated PA. The recurrence of disease in two cases with a further response to lower dose cyclophosphamide has implications for the optimal duration of therapy for these low grade, aggressive tumors.

Antineoplastic Agents, Alkylating↗
PubMed1996

Repair analysis of 4-hydroperoxycyclophosphamide-induced DNA interstrand crosslinking in the c-myc gene in 4-hydroperoxycyclophosphamide-sensitive and -resistant medulloblastoma cell lines.

Cyclophosphamide is one of the most active agents in the treatment of medulloblastoma. However, development of resistance to this alkylator frequently occurs and is the harbinger of tumor progression and death. In order to understand the biochemical basis of this resistance, we generated a panel of medulloblastoma cell lines in our laboratory that were resistant to 4-hydroperoxycyclophosphamide (4-HC). Previously, we have shown that elevated levels of aldehyde dehydrogenase and glutathione mediate cellular resistance to 4-HC. The present study was conducted to identify the third unknown mechanism mediating the resistance of cell line D283 Med (4-HCR) to 4-HC, testing the hypothesis that this resistance is mediated by an increased repair of DNA interstrand crosslinks (ICLs). The doses of 4-HC that produced a one- and two-log cell kill of D283 Med cells were 25 and 50 microM, respectively, compared with values of 125 and 165 microM in D283 Med (4-HCR), the resistant cell line. The formation and disappearance of 4-HC-induced DNA ICLs at the c-myc gene were subsequently studied by DNA denaturing/renaturing gel electrophoresis and Southern blot analysis. 4-HC-induced DNA ICLs in the c-myc gene exhibited a dose-dependent relationship. The percentage of the c-myc gene that was crosslinked was approximately 1-3% at a dose of 100 microM. More than 50% of the DNA crosslinking in D283 Med (4-HCR) cells was removed by 6 h after drug treatment, whereas, in D283 Med cells, more than 90% of the DNA crosslinking was still present at 6 h. These findings suggest that the increased repair of DNA ICLs in D283 Med (4-HCR) may contribute significantly to its resistance to 4-HC.

Blotting, Southern↗
PubMed1996

In vivo growth conditions suppress the expression of ganglioside GM2 and favour that of lacto series gangliosides in the human glioma D-54MG cell line.

The human glioma D-54MG cell line grown in vitro primarily expresses ganglio series gangliosides, particularly GM2. Subcutaneous injection of these cells into nude mice produced xenografts with an increased content of the human glioma-associated lacto series gangliosides, primarily 3'-isoLM1, an alteration that was dose dependent, with the highest dose (1 x 10(8)) resulting in a phenotype that was most like that of the inoculum. After one passage in vivo, the lacto series dominated and reached a proportional level that was kept throughout the 10 passages. The mRNA levels of the GM2-synthase clearly coincided with GM2 expression and was 20 times higher in cells grown in vitro than in those grown in vivo. These results support the view that ganglioside expression in human gliomas is strongly influenced by environmental factors.

Animals↗
PubMed1996

Enhancement of melphalan activity by inhibition of DNA polymerase-alpha and DNA polymerase-beta.

Our previous studies exploring melphalan resistance in the human rhabdomyosarcoma xenograft TE-671 MR revealed elevation of DNA polymerase-alpha and DNA polymerase-beta. The present study evaluated the alteration of melphalan activity in TE-671 (melphalan-sensitive) and TE-671 MR (melphalan-resistant) subcutaneous xenografts in nude mice after DNA polymerase-alpha was inhibited using aphidicolin glycinate (AG) and DNA polymerase-beta was inhibited using dideoxycytidine (DDC). Administration of AG or DDC did not produce toxicity or demonstrate antineoplastic activity when given alone. AG (90 mg/m2) enhanced the activity of melphalan against TE-671, with growth delays increasing by 8.4, 15.8, and 21.2 days over the regimen with melphalan only. AG (180 mg/m2) only modestly increased melphalan activity against TE-671 MR, with the growth delays increasing from 9.6 and 12.1 days using melphalan alone to 12.1 and 14.5 days using melphalan plus AG. AG (180 mg/m2) plus melphalan (the dose lethal to 10% of animals) produced greater weight loss compared with melphalan alone, whereas DDC plus melphalan produced no additional toxicity. DDC modestly enhanced the activity of melphalan plus AG against TE-671 MR. AG plus O6-benzylguanine did not increase the activity of 1,3-bis(2-chloroethyl)-1-nitrosourea against TE-671 or TE-671 MR. AG (90 mg/m2 and 180 mg/m2) inhibited DNA polymerase-alpha to 80% and 72% of control in TE-671 and 64% and 37% in TE-671 MR, and DDC inhibited DNA polymerase-beta to 59% in TE-671 and 48% in TE-671 MR. These results suggest a role for AG-mediated enhancement of melphalan activity, particularly in the treatment of newly diagnosed, melphalan-sensitive tumors.

Animals↗
PubMed1996

Chimeric anti-tenascin antibody 81C6: increased tumor localization compared with its murine parent.

When labeled using the Iodogen method, a chimeric antibody composed of the human IgG2 constant region and the variable regions of murine anti-tenascin 81C6 exhibited superior uptake in human glioma xenografts compared with its murine parent. In the current study, three paired-label experiments were performed in athymic mice with subcutaneous D-54 MG human glioma xenografts to evaluate further the properties of radioiodinated chimeric 81C6. These studies demonstrated that (a) the enhanced tumor uptake of chimeric 81C6 is specific; (b) when labeling was performed using N-succinimidyl 3-iodobenzoate, chimeric 81C6 again showed preferential accumulation in tumor compared with murine 81C6; and (c) the tumor uptake advantage observed previously with murine 81C6 for N-succinimidyl 3-iodobenzoate compared with Iodogen labeling did not occur with chimeric 81C6.

Animals↗
PubMed1996

Production and characterization of two ependymoma xenografts.

Childhood ependymomas exhibit epidemiologic, anatomic, histologic, and biologic features and distinguish them from other gliomas. Because of their propensity to grow in functionally sensitive regions of the brain, adequate tumor sampling for basic and therapeutic research is limited. We have established xenografts in both subcutaneous and intracranial nude mouse systems (D528 EP-X, D612 EP-X) from the ependymomas of two nonrelated children. Median subcutaneous growth rates (reported in days to grow from 200 mm3 to 1000 mm3) are 82 days for D528 EP-X (n = 10) and 50 days for D612 EP-X (n = 10). D528 EP-X grows intracranially with a median postimplantation survival of 85 days (n = 10); D612 EP produces a median postimplantation survival of 72.5 days (n = 10). Both xenografts grow as well-formed masses with no evidence of infiltration into either brain or subcutaneous tissues. While perivascular pseudopalisading is found in both xenografts, true ependymal rosette formation is absent. Ultrastructurally, neither xenograft exhibits cilia, but both produce abundant intermediate filaments. By light microscopy, the neoplastic cells are immunoreactive for the intermediate filaments glial fibrillary acidic protein, vimentin, and nestin. Karyotypically D528 EP exhibits 46,XX,del(6)(q22q26)/46,XX while D612 EP exhibits 50,XX, +X,t(1;8)(p11;q11),t(1;8)(p11;q11), +1,-4, der(5)t(4;5)(q12;q35), +der(5)t(4;5)(q12;q35),-6, +9, +9,-16, +der(17)t(6;17)(p11;p11), +mar. Restriction fragment length polymorphism studies comparing the primary brain tumor tissue from each patient against multiple passages of the resulting xenografts confirm the origin of both xenografts. These xenografts represent models on which future studies into the oncogenesis, progression and therapy of ependymomas can be performed.

Animals↗
PubMed1996

Primary brain tumor incidence rates in four United States regions, 1985-1989: a pilot study.

There has been controversy in the last decade over whether the reported increase in brain tumors reflects a real increase in incidence rates. Incidence data on the full spectrum of brain tumors is lacking in the discussion since current cancer reports in the United States are restricted to malignant tumors. Data on tumors from four population-based cancer registries in the United States were compiled to provide incidence rates of benign and malignant brain tumors and to assess the feasibility of providing these data on a larger scale. A total of 8,070 primary tumors diagnosed from 1985 to 1989 in Connecticut, Massachusetts, Missouri and Utah were obtained. Brain tumors were defined using the International Classification of Diseases for Oncology codes 191.0-191.9, 192.0-192.3, 192.8-192.9 and 194.3-194.4. Stratum-specific incidence rates by location and histology were estimated by sex, age and region. Age-adjusted rates were standardized to the 1970 United States population. An age-adjusted incidence rate of 9.4/10(5) was observed, which reflects a 36% increase in males and a 68% increase in females over the rate based on malignant tumors alone from the Surveillance, Epidemiology and End Results cancer reporting system. Incorporating benign tumors into cancer registry data would increase the reported incidence rates primarily in females and for meningiomas and nerve sheath tumors. This expanded incidence rate represents a substantial improvement in the ability to describe the occurrence of these complex tumors by subtype with a modest increase in overall case registrations for cancer registries. Centralization of data on all brain tumors appears feasible. Variations in histology-specific rates across regions raises questions that need to be addressed about the ascertainment and accuracy of tumor classification. Use of the cancer registration system to improve the reporting of brain tumors in the United States is important to our understanding of the occurrence of these complex tumors and to our ability to conduct large-scale epidemiologic investigations.

Adolescent↗
PubMed1996

Radioimmunotherapy with alpha-particle emitting radioimmunoconjugates.

Radionuclides which decay by the emission of alpha-particles are attractive for certain radioimmunotherapeutic applications. These include the treatment of lymphomas, compartmentally spread malignancies such as ovarian cancer and neoplastic meningitis, and micrometastatic disease. Two alpha-emitting radionuclides of interest for this purpose are 212Bi (60.6 min half life) and 211At (7.2 hr half life). Compared with the beta-emitters commonly used for radiotherapy, the alpha-particles of 212Bi and 211At are of higher energy, much shorter range (less than 100 microm), and considerably higher linear energy transfer. Preliminary results obtained in a variety of in vitro systems and in vivo models have documented the exquisite toxicity of alpha-particles and have established a basis for initiating radiotherapy trials in humans with monoclonal antibodies labeled with alpha-emitting radionuclides.

Alpha Particles↗
PubMed1996

Intrathecal 131I-labeled antitenascin monoclonal antibody 81C6 treatment of patients with leptomeningeal neoplasms or primary brain tumor resection cavities with subarachnoid communication: phase I trial results.

We aimed to determine the maximum tolerated dose (MTD) of 131I-labeled 81C6 in patients with leptomeningeal neoplasms or brain tumor resection cavities with subarachnoid communication and to identify any objective responses. 81C6 is a murine IgG monoclonal antibody that reacts with tenascin in gliomas/carcinomas but does not react with normal adult brain. 131I-labeled 81C6 delivers intrathecal (IT) radiation to these neoplasms. This study was a Phase I trial in which patients were treated with a single IT dose of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating doses of 131I (starting dose, 40 mCi; 20 mCi escalations) on 10 mg 81C6. MTD is defined as the highest dose resulting in serious toxicity in no more than two of six patients. Serious toxicity is defined as grade III/IV nonhematological toxicity or major hematological toxicity. We treated 31 patients (8 pediatric and 23 adult). Eighteen had glioblastoma multiforme. Patients were treated with 131I doses from 40 to 100 mCi. Hematological toxicity was dose limiting and correlated with the administered 131I dose. No grade III/IV nonhematological toxicities were encountered. A partial response occurred in 1 patient and disease stabilization occurred in 13 (42%) of 31 patients. Twelve patients are alive (median follow-up, > 320 days); five are progression free >409 days median posttreatment. The MTD of a single IT administration of 131I-labeled 81C6 in adults is 80 mCi 131I-labeled 81C6. The MTD in pediatric patients was not reached at 131I doses up to 40 mCi normalized for body surface area.

Adolescent↗
PubMed1995

A structural basis for a phosphoramide mustard-induced DNA interstrand cross-link at 5'-d(GAC).

Phosphoramide mustard-induced DNA interstrand cross-links were studied both in vitro and by computer simulation. The local determinants for the formation of phosphoramide mustard-induced DNA interstrand cross-links were defined by using different pairs of synthetic oligonucleotide duplexes, each of which contained a single potentially cross-linkable site. Phosphoramide mustard was found to cross-link dG to dG at a 5'-d(GAC)-3'. The structural basis for the formation of this 1,3 cross-link was studied by molecular dynamics and quantum chemistry. Molecular dynamics indicated that the geometrical proximity of the binding sites also favored a 1,3 dG-to-dG linkage over a 1,2 dG-to-dG linkage in a 5'-d(GCC)-3' sequence. While the enthalpies of 1,2 and 1,3 mustard cross-linked DNA were found to be very close, a 1,3 structure was more flexible and may therefore be in a considerably higher entropic state.

Base Sequence↗
PubMed1995

Tumor-specific anti-epidermal growth factor receptor variant III monoclonal antibodies: use of the tyramine-cellobiose radioiodination method enhances cellular retention and uptake in tumor xenografts.

Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene are characteristics of many types of tumors. One class of EGFR mutations, EGFRvIII, is characterized by an in-frame deletion resulting in a truncated external domain of the receptor. EGFRvIII was first identified in a subset of gliomas and has since been found in some non-small cell lung carcinomas and breast carcinomas. mAbs specific for this variant form of EGFR but unreactive with the wild-type EGFR have been reported from our laboratory. This study further characterizes three of these antibodies. We determined, via radiolabeling techniques and immunofluorescence microscopy, that, after cell binding in vitro, the anti-EGFRvIII-specific mAbs internalize at 37 degrees C. Furthermore, subsequent to internalization, the antibodies were processed intracellularly, presumably by lysosomal degradation. We also examined the use of an alternative radiolabeling procedure that uses nonmetabolizable radio-iodinated tyramine cellobiose. Our results show that the tyramine cellobiose labeling method allows for greater tumor cell retention of radiolabel in vitro (76% for tyramine cellobiose and 27% for Iodo-Gen after 24 h). Paired-label biodistribution studies in athymic mice indicate that anti-EGFRvIII mAb L8A4 localizes specifically to EGFRvIII-expressing tumor xenografts with a maximum of 34.3 +/- 7.6% injected dose/g when labeled using tyramine cellobiose compared with a maximum of 14.9 +/- 4.3% injected dose/g using Iodo-Gen; similar results were obtained with mAb H10. These results suggest that the anti-EGFRvIII mAbs may serve as potential carriers for radioconjugate- and immunotoxin-based therapies for tumors expressing EGFRvIII.

Animals↗
PubMed1995

Intraarterial administration of melphalan for treatment of intracranial human glioma xenografts in athymic rats.

Malignant gliomas will affect 15,000-17,000 Americans each year and carry a dismal prognosis. Adjuvant chemotherapy is hampered by inadequate drug delivery, systemic toxicity, and a markedly variable biological sensitivity. Intraarterial (i.a.) therapy may enhance selectivity by improving tumor drug delivery and reducing systemic toxicity. Using melphalan given i.a., we studied the therapy of intracranial human glioma xenografts in male athymic nude rats (mean weight, 300 g) which were inoculated intracerebrally with D-54 MG and D-456 MG. On Days 6 and 7 (D-54 MG) or Days 9 and 10 (D-456 MG), rats randomized by body weight and treated with single-dose melphalan given i.a. at 0.5 or 0.75 mg produced significantly higher median survival (D-54 MG, Days 33 and 32; D-456 MG, Days 52 and 54, respectively) compared with i.a. saline (D-54 MG, Day 14, P < 0.001; D-456 MG, Day 24, P = 0.000) or melphalan given i.v. at 0.75 mg and 0.9 mg (D-54 MG only; Day 19, P < 0.001; Day 23, P < 0.001, respectively) and at 0.5 and 0.75 mg (D-456 MG only; Day 26 for both doses, P = 0.00). Although a dose-dependent increase in median survival (D-54 MG, 0.25 mg, Day 18; 0.5 mg, Day 28.5; 0.75 mg, Day 32.5) was observed with i.a. administered melphalan, no significant difference was apparent between 0.5 and 0.75 mg in either tumor model (D-54 MG, P = 0.15; D-456 MG, P = 0.37). Toxicity studies in nontumor-bearing athymic rats yielded a maximum tolerated dose of 0.8 mg for i.a. administered melphalan. This dosage was superior in spite of different xenograft permeabilities (apparent mean blood-to-tissue transport [K] values for alpha-aminoisobutyric acid, 5.8 for D-54 MG and 1.3 for D-456 MG). Pharmacokinetic experiments demonstrated a significant first pass advantage for i.a. (versus i.v.) melphalan. The short plasma half-life, marked antiglioma activity, and lack of requirement for metabolic activation indicate that i.a. melphalan holds considerable promise for human glioma therapy.

Animals↗
PubMed1995

Activity of temozolomide in the treatment of central nervous system tumor xenografts.

The activity of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin- 4(3H)-one (temozolomide) in the treatment of a panel of xenografts derived from ependymoma, medulloblastoma, and childhood and adult high-grade glioma was evaluated in athymic nude mice bearing s.c. and intracranial tumors. Temozolomide administered daily for a total of five doses demonstrated marked activity against a panel of Mer+ xenografts despite marginal to moderate activity of 1,3-bis(2-chloroethyl)-1-nitrosourea. The growth delays produced by temozolomide in these xenografts were 1.8-7.5-fold greater than those produced by procarbazine. Although temozolomide demonstrated marginal activity against the Mer+ cell line D341 Med when a 5-day schedule was used, a high-dose 1-day schedule resulted in moderate activity. Temozolomide produced increases in median survival of 1285% (adult glioma D-54 MG), 323% (childhood glioma D-456 MG), and 68% (ependymoma D612 EP). Pretreatment of mice with O6-benzylguanine increased temozolomide-induced mortality, requiring reduction of the dosage from 1200 to 750 mg/m2 on the single-day regimen. O6-Benzylguanine pretreatment of mice bearing Mer+ D341 Med increased the growth delay of temozolomide, in duplicate experiments, from -3.1 to 4.8 and 1.1 to 4.9 days. These studies suggest that temozolomide may be active in the treatment of a broad spectrum of central nervous system cancers, including Mer+ tumors resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea.

Animals↗
PubMed1995

Chromosome 10 deletion mapping in human gliomas: a common deletion region in 10q25.

The high incidence of loss of chromosome 10 alleles in glioblastoma multiforme suggests the presence on this chromosome of a tumor suppressor gene that is important in glioma tumorigenesis and progression. Our initial deletion mapping studies using restriction fragment length polymorphism markers indicated a common deletion region in 10q24-qter. In an attempt to localize the deleted region further, we screened a panel of 117 gliomas for loss of heterozygosity for chromosome 10 loci using 10 microsatellite markers. Seventeen tumors showed partial loss of a copy of chromosome 10 and were further analysed using 28 additional microsatellite markers. Of these, 10 had terminal deletion in the q arm, three had deletions in both p and q arms, two contained interstitial deletion in 10q and two carried deletions in 10p. In the 15 tumors with deletions in 10q, the minimal overlapping deletion region was in distal 10q between markers D10S587 and D10S216. Loci D10S587 and D10S216 are approximately mapped to a 5 cM region in 10q25.1.

Brain Neoplasms↗
PubMed1995

Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model.

LMB-7 [B3(Fv)-PE38] is a single-chain immunotoxin constructed from the murine monoclonal antibody B3 and a truncated from of Pseudomonas exotoxin PE38. Antibody B3 recognizes a carbohydrate epitope found on solid tumors that frequently invade the intrathecal space and cause neoplastic meningitis. We tested the therapeutic value of intrathecally administered LMB-7 by using a model of human neoplastic meningitis in athymic rats. This model is representative of a clinical situation in that antibody B3 cross-reacts with a number of normal tissues that can be used to monitor potential systemic toxicity. Treatment was begun 3 days after A431 tumor implantation. Without treatment, the animals median survival was 10 days. Intrathecal administration of 10 micrograms of LMB-7 in 40 microliters on days 3, 5, and 7 produced 4 of 10 and 8 of 10 long-term survivors (> 170 days) in two experiments. Of the long-term survivors, 2 of 4 and 7 of 8 survivors had no microscopic evidence of tumor and were considered histologic cures. Lack of significant toxicity in the effective dose range and specificity make LMB-7 an excellent candidate for intrathecal treatment of neoplastic meningitis in humans.

Animals↗
PubMed1995

Tumor antigens in astrocytic gliomas.

Gliomas affect 15,000 to 17,000 Americans every year and carry a dismal prognosis. The potential of immunologically mediated diagnosis and therapy, although greatly enhanced since the advent of monoclonal antibodies, has not been fully realized due to significant problems, most especially the challenge of identifying antigenic molecules specific to glial tumors. Other problematic issues include antigen-associated factors such as heterogeneity, modulation, shedding, and cross-reactivity with normal cells, and factors associated with therapeutic agent delivery, typically variable tumor perfusion and unfavorable diffusional forces in tumor microenvironment. An understanding of these problems called for the delineation of operationally specific antigens (tumor-associated antigens not expressed by the normal central nervous system) combined with the use of compartmental therapeutic approaches to increase the specificity of therapy. Numerous antigens have been identified and are classified as extracellular/matrix-associated, membrane-associated, and intracellular antigens. Nevertheless, only a few have been demonstrated to be of significant therapeutic and diagnostic utility. These few include the extracellular matrix-associated antigens tenascin and GP 240, defined by the monoclonal antibodies 81C6 and Mel-14, both of which are now in Phase I clinical trials, and membrane-associated ganglioside molecules, primarily 3', 6'-isoLD1, defined by the antibody DMAb-22. Recent identification of the overexpression of a deletion variant of the epidermal growth factor receptor (EGFRvIII) in up to 50% of the more malignant glial tumors and the subsequent creation of monoclonal antibodies that are specific to this molecule and do not recognize the wild-type EGFR provide the most exciting development yet in the design of specific antiglioma immunoconjugates. In addition, the tumor-specific nature of EGFRvIII combined with improved knowledge of immune mechanisms, especially in the context of the central nervous system, will facilitate the design of highly selective cell-mediated therapeutic approaches with a view toward obtaining tumor-specific immunity.

Animals↗