Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal antibody I-131 MOv18: Clinical results in patients with minimal residual disease of ovarian cancer

Crippa, Flavio; Bolis, Giorgio; Seregni, Ettore; Gavoni, Nicoletta; Scarfone, Giovanna; Ferraris, Cristina; Buraggi, G.L.; Bombardieri, Emilio

doi:10.1016/0959-8049(94)00454-d

Cited by 79 publications

(48 citation statements)

References 14 publications

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“…These studies indicate that the decreased energy absorption in smaller tumours is compensated by the higher tumour uptake of MAbs. Also, recent results from clinical RIT studies using intraperitoneally administered 186Re-labelled NR-LU-10 IgG or '311-labelled MAb MOvl8 in adjuvant therapy of ovarian cancer patients showed that RIT may be particularly effective in eradicating minimal residual disease (Jacobs et al, 1993, Crippa et al, 1995. These dosimetry estimations indicate the feasibility of adjuvant RIT with radiolabelled E48 IgG or U36 IgG in head and neck cancer patients.…”

Section: British Journal Of Cancermentioning

confidence: 95%

Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients

Bree

Roos²,

Plaizier

et al. 1997

Br J Cancer

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Summary Preliminary data from recent clinical radioimmunoscintigraphy studies indicate that 99mTc-labelled murine monoclonal antibodies (MAbs) E48 and U36 have a similar ability to target squamous cell carcinoma of the head and neck (HNSCC) selectively. In the present study we describe additional aspects of murine and chimeric MAb (mMAb and cMAb) E48 and U36, which might influence the selection of one MAb for adjuvant radioimmunotherapy. To make direct comparison possible, ten patients received 11.2 ± 0.3 and 11.1 ± 0.2 mg (n = 5) or 51.1 ± 0.1 and 51.0 ± 0.4 mg (n= 5) of both mE48 IgG and mU36 IgG labelled with 1311 and 1251 simultaneously and underwent surgery 7-8 days after injection. The mean uptake of iodine-labelled mE48 IgG and mU36 was highest in tumour tissue, 8.9 ± 8.9 and 8.2 ± 4.4 %ID kg-' respectively. Tumour to non-tumour ratios for oral mucosa, skin, muscle, blood and bone marrow aspirate were 2.5, 5.5, 25.2, 4.7 and 4.0 respectively in the case of mE48 IgG and 2.3, 4.1, 21.0, 5.8 and 5.8 respectively in the case of mU36 IgG. The distribution of mMAbs E48 and U36 throughout tumours that had been collected in previous studies was heterogeneous when administered at a dose of 1 or 12 mg, and homogeneous when administered at a dose of 52 mg. Administration of mE48 IgG (1-52 mg) resulted in a human anti-mouse antibody response in 12 out of 28 patients, while for mU36 IgG (1-52 mg), this figure was three out of 18 patients. cMAb E48 was shown to be highly effective in mediating antibody-dependent cellular cytotoxicity in vitro, while cMAb U36 and mMAbs E48 and U36 were not effective at all. Rationales are provided that give priority to the start of adjuvant radioimmunotherapy trials with 1'6Re-labelled cMAb U36 IgG in head and neck cancer patients who are at high risk for the development of locoregional recurrences and distant metastases.Keywords: monoclonal antibodies; head and neck cancer; squamous cell carcinoma; biodistribution; human anti-mouse antibody response; antibody-dependent cellular cytotoxicityDuring 1996 approximately 41 090 Americans will develop head and neck cancer and 12 510 will die from it. Worldwide more than 500 000 new cases are projected annually, and the incidence is rising. In head and neck cancer, squamous cell carcinoma accounts for approximately 90% of all tumours (Parker et al, 1996). About one-third of these patients present with early-stage (I and II) head and neck squamous cell carcinoma (HNSCC), while two-thirds present with advanced disease (stage III and IV) (Vernham and Crowther, 1994). Although early-stage HNSCC can, in the great majority of cases, be cured with surgery or radiotherapy alone, the local failure rate after surgery and/or radiotherapy in advanced stages is more than 50%. Moreover, about 25% of these patients develop distant metastases (Stupp et al, 1994).Despite an increase in the locoregional control of HNSCC, owing to improved surgery and radiotherapy, current therapy regimens have failed to increase the 5-year survival rate in HNSCC patients (Pa...

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Section: British Journal Of Cancermentioning

confidence: 95%

Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients

Bree

Roos²,

Plaizier

et al. 1997

Br J Cancer

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“…9 These Mab, and their chimeric or bispecific derivatives, were entered in several diagnostic and therapeutic trials with some relevant clinical responses. 20,21 To gain insight into the role of FR in ovarian cancer progression, we exploited the specificity of the anti FR MOV19 Mab to construct a single-chain (sc)Fv intrabody and tested the effects of functional downregulation of FR membrane expression on ovarian tumor cell proliferation and adhesion.…”

Section: Introductionmentioning

confidence: 99%

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

et al. 2003

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The a-folate receptor (FR) is selectively overexpressed in 90% of nonmucinous ovarian carcinomas, whereas no expression is detectable in normal ovarian surface epithelium (OSE). Indirect evidence suggests that FR expression is associated with tumor progression and affects cell proliferation. To evaluate better the role of FR, we developed an approach based on intracellular expression of single-chain (sc) antibodies (intrabody) to downmodulate membrane expression of FR in ovary cancer cells. IGROV-1 and SKOV3 ovarian carcinoma cell lines were transfected with an anti-FR intrabody. Transfectants and parental cells were tested for FR, integrins and anti-FR intrabody expression by fluorescence-activated cell sorting (FACS), reverse transcription and polymerase chain reaction (RT-PCR) and/or immunoblotting. Cell growth characteristics and adhesion properties were evaluated in liquid, semisolid and organotypic cultures. The anti-FR scFv inhibited FR expression from 60 to 99%. At physiological concentrations of folate, proliferation varied directly as a function of FR expression. FR downmodulation was accompanied by reduced colonyforming ability in soft agar, morphological change of the cells, significant enhanced adhesion to laminin or Matrigel, a twoto three-fold increase in a6b4 integrin expression, and a marked reduction in laminin production. In three-dimensional organotypic cultures, anti-FR intrabody-transfected IGROV1 cells grew as a single-ordered layer, reminiscent of normal OSE growth in vivo. In conclusion, the anti-FR intrabody reverses the transformed phenotype in ovary cancer cells and may provide an efficient means to inhibit selectively the growth of these cells.

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“…In fact, the FR␣ overexpression in human ovarian carcinomas seems to be an early event during the transformation process, and is maintained or even increased during tumor progression, suggesting that this molecule is essential for tumor cell life. 25 Moreover, no Ag loss variants could be detected in patients whose disease relapsed after passive immunotherapy with anti-FR␣ mAb 26 or after adoptive transfer of lymphocytes retargeted with anti-FR␣/anti-CD3 bispecific mAb. 27 In conclusion, our data indicate that human FR␣ DNA vaccination is effective in mice and may deserve further investigations to evaluate its possible application for immunotherapy of human ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In a radioimmunotherapeutic trial, 5 of 16 ovarian carcinoma patients showed a complete response after intraperitoneal radioimmunotherapy with 131 I-labeled anti-FR␣ MOv18. 26 In addition, a clinical phase I/II trial of T-cell retargeting by bispecific anti-CD3/anti-FR␣ mAb showed tumor regression in 27% of ovarian carcinoma patients at advanced stages of the disease. 27 Limitations of this approach included activity restricted to the peritoneal cavity and the need for in vitro preactivation of the effector cells, thus limiting the routine application of this procedure.…”

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confidence: 99%

DNA vaccination against the ovarian carcinoma-associated antigen folate receptor α (FRα) induces cytotoxic T lymphocyte and antibody responses in mice

et al. 1999

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Human folate receptor ␣ (FR␣) is a folate-binding protein that is selectively overexpressed in ovarian carcinoma and has been regarded as a suitable target antigen for immunotherapy purposes. To study the possible use of this antigen in DNA vaccination, FR␣ cDNA was ligated into the VR1012 (Vical) expression vector under the transcriptional control of the cytomegalovirus promoter. A total of 100 g of purified plasmid DNA was injected intramuscularly in BALB/c mice three times at 14-day intervals. At 10 days after the second injection, the sera of the animals (100%) displayed significant antibody titers (by indirect immunofluorescence and fluorescence-activated cell sorter analysis) against syngeneic C26 cells transduced with FR␣, but not against unmodified C26 cells. Immunoglobulin G2a was the predominant isotype. In addition, specific cytotoxic T lymphocyte activity against FR␣-transduced C26 cells could be detected in splenocytes from all immunized animals. Coinjection of a plasmid containing interleukin-2 cDNA increased both antibody titers and cytotoxic T lymphocyte activity. Challenge by subcutaneous injection with FR␣-transduced C26 cells (performed 10 days after the third injection) showed a statistically significant delay in tumor growth. Vaccination with the FR␣ and interleukin-2 cDNA mixture, which was performed after an intravenous injection of FR␣-transduced cells, enhanced the mean survival time and reduced the number of lung metastases, thus suggesting that such vaccination is effective even against preexisting tumor cells.

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Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal antibody I-131 MOv18: Clinical results in patients with minimal residual disease of ovarian cancer

Cited by 79 publications

References 14 publications

Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients

Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

DNA vaccination against the ovarian carcinoma-associated antigen folate receptor α (FRα) induces cytotoxic T lymphocyte and antibody responses in mice

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