Determination of the immunoreactive function of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess

Lindmo, Tore; Boven, Epie; Cuttitta, Frank; Fedorko, Joseph; Bunn, Paul A.

doi:10.1016/0022-1759(84)90435-6

Cited by 798 publications

(558 citation statements)

References 15 publications

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“…Immunoreactivity, i.e. the proportion of radiolabelled antibody that would bind antigen at infinite antigen excess, was determined using a protocol similar to that described by Lindmo et al (1984).…”

Section: Control Antibodies Used In This Investigationmentioning

confidence: 99%

The human EGF receptor as a target for cancer therapy: six new rat mAbs against the receptor on the breast carcinoma MDA-MB 468

Modjtahedi

Styles²,

Cj³

1993

Br J Cancer

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(Santon et al., 1986;Ozanne et al., 1986;Velu et al., 1987; Difore et al., 1987;Harris et al., 1990). In addition, some of these tumours produce ligands for the receptor and it has been suggested that an autocrine mechanism is involved in progression of cancers of this type (Sporn & Roberts 1985;Imanishi et al., 1988;Nistar et al., 1988; Dernyck 1990;Tateishi et al., 1990;Yoshida et al., 1990; Morishige et al., 1991). Over-expression of the EGFR by tumour cells, compared to their normal counterparts, has been reported for a number of squamous cell carcinomas (e.g. Cowley et Hendler et al., 1984;Sainsbury et al., 1985;Gullick et al., 1986) and this in turn was also correlated to poor prognosis in patients with some of these carcinomas (reviewed by Gullick, 1991 We have reported (Modjtahedi, et al., 1992) the preparation and properties of ten rat mAbs that bind to three distinct epitopes (A,B,C) on the external domain of the EGFR using as immunogen the human squamous cell carcinoma HN5. While all of the mAbs against epitopes B and C blocked the binding of EGF and TGFa to the receptor on a number of squamous carcinoma cell lines the antibodies against epitope C were an order of magnitude better than the others at inhibiting cell growth. The best antibody, ICR16, inhibited completely the growth of HN5 cells in vitro at antibody concentrations above 1 nM. However, none of the antibodies was of the IgG2b isotype and therefore would not be expected to interact efficiently with the host immune effector functions in rat, mouse or man. Since our intention is to test the effectiveness of antibodies in the clinic we report here the preparation of a second series of antibodies using as immunogen the EGFR over-expressing breast carcinoma (Filmus et al., 1985) searching particularly for IgG2b antibodies with growth inhibitory properties. Materials and methods Cell lines

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Section: Control Antibodies Used In This Investigationmentioning

confidence: 99%

The human EGF receptor as a target for cancer therapy: six new rat mAbs against the receptor on the breast carcinoma MDA-MB 468

Modjtahedi

Styles²,

Cj³

1993

Br J Cancer

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“…The immunoreactive fraction of each MoAb preparation was determined using a modified LINDMO assay with an excess of human brain homogenate (Lindmo et al, 1984). Non-specific binding to brain was determined using an isotype matched control antibody and occasionally also confirmed by blockade of "3'I-ERIC-1 binding with a gross excess of non-radiolabelled antibody.…”

Section: Methodsmentioning

confidence: 99%

Treatment of recurrent and cystic malignant gliomas by a single intracavity injection of 131I monoclonal antibody: feasibility, pharmacokinetics and dosimetry

Papanastassiou

Pizer²,

Coakham³

et al. 1993

Br J Cancer

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“…Dosimetric and therapeutic 131 I-labelling of tositumomab was performed centrally (MDS Nordion Inc., Kanata, Canada) and the labelled compound was shipped frozen on a per patient basis. Two arbitrarily selected therapeutic batches of 131 I-tositumomab were analysed for immunoreactivity using the Lindmo approach (Lindmo et al, 1984). Immunoreactivity was measured immediately after upfreezing the batches for injection of patients.…”

Section: Dosimetric and Therapeutic Antibody Administrationsmentioning

confidence: 99%

“…About 6 ng 131 I-tositumomab were incubated for 2 h at 371C with five serial dilutions of 1 -10 Â 10 6 fresh, exponentially grown Raji or Daudi B lymphoma cells in duplicates. Cell-bound activity was determined and expressed in % of incubated activity, specific binding, after subtraction of nonspecific binding, was determined and expressed as percent of incubated activity and immunoractivity determined using double inverse plot (Lindmo et al, 1984) with extrapolation at infinite antigen excess.…”

Section: Dosimetric and Therapeutic Antibody Administrationsmentioning

confidence: 99%

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

et al. 2006

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We present the long-term results of 18 chemotherapy relapsed indolent (N ¼ 12) or transformed (N ¼ 6) NHL patients of a phase II anti-CD20 131 I-tositumomab (Bexxar s ) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with 131 I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, 131 I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46 -70 months.

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Determination of the immunoreactive function of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess

Cited by 798 publications

References 15 publications

The human EGF receptor as a target for cancer therapy: six new rat mAbs against the receptor on the breast carcinoma MDA-MB 468

The human EGF receptor as a target for cancer therapy: six new rat mAbs against the receptor on the breast carcinoma MDA-MB 468

Treatment of recurrent and cystic malignant gliomas by a single intracavity injection of 131I monoclonal antibody: feasibility, pharmacokinetics and dosimetry

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

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