Specific detection of anti-idiotypic immune responses in cancer patients treated with murine monoclonal antibody

The monoclonal antibody-defined, tumorassociated antigen GA733 was purified from the SW948 human colorectal carcinoma cell line and its partial amino acid sequence was determined. By using a synthetic oligonucleotide probe, two recombinants were isolated from a total human genomic library. We prove the existence of a family of GA733 genes. One of the genomic isolates is demonstrated to be an intronless gene, which is transcribed in pancreatic carcinoma cell lines and in placenta. The GA733 proteins were observed to contain sequences homologous to a repeat unit occurring 10 times in thyroglobulin and once in the HLA-DR-associated invariant chain. A more evolutionarily distant relationship was found with the a chain of the interleukin 2 growth factor receptor.Monoclonal antibodies (mAbs) C017-1A and the related GA733 (1) have been extensively evaluated for the diagnosis and therapy of human gastrointestinal tumors. These mAbs were derived from the immunization of mice with a human colorectal adenocarcinoma cell line and a stomach adenocarcinoma cell line, respectively.

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“…6). 7 Upper, lanes 2 and 3) relative to the colorectal carcinoma cell line SW948 (Fig. 7 Upper, lane 1).…”

Section: Resultsmentioning

confidence: 99%

“…When human subjects with gastrointestinal adenocarcinoma were inoculated with mAb C017-1A (Abl), many of the patients produced anti-idiotype antibody (Ab2) that reacted with the binding site of the Abl (6,7). In theory, the administration of internal image Ab2 alone may effect an antitumor response.…”

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confidence: 99%

Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733.

Linnenbach

Wojcierowski

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

109

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“…Sci. USA 88 (1991) Abl-treated patients, since the Ab2 concentration can reach over 40 ,ug/ml in the blood (12,13). In several studies, it was observed that the clinical anti-tumor response in patients treated with Abl to various TAA correlated with the presence of Ab2 (25,27).…”

Section: Discussionmentioning

confidence: 99%

“…Some clinical trials have been initiated in which Ab2 were generated in animals (goat or mouse) to be administered to human cancer patients (10,11). Humans can also represent a potential source ofAb2; indeed, cancer patients receiving an anti-TAA of animal origin will usually produce antibodies to this Abl and these anti-immunoglobulin antibodies will include both antibodies to the constant regions and Ab2 (12,13). In this report, we show that Ab2,B mimicking a carcinoembryonic antigen (CEA) epitope are produced by a patient treated with NP-4, a murine monoclonal antibody to CEA.…”

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confidence: 99%

Human response against NP-4, a mouse antibody to carcinoembryonic antigen: human anti-idiotype antibodies mimic an epitope on the tumor antigen.

Losman¹,

Hansen²,

Sharkey³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Anti-idiotype antibodies (Ab2) were purified from a cancer patient treated with NP-4, a murine monoclonal antibody to carcinoembryonic antigen (CEA). These Ab2 were specific for NP4 and inhibited the binding between NP4 and CEA. BALB/c mice immunized with these human Ab2 produced anti-Ab2 antibodies that were also reactive with the CEA epitope recognized by NP4. These results indicate that human Ab2 to NP-4 can antigenically mimic the CEA epitope recognized by NP4.

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“…They are now used for in vivo diagnosis and therapy in many situations, and the development of human antibodies against both the constant and variable regions of mouse immunoglobulin has been well documented (1,2).…”

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confidence: 99%

Characteristic immunophenotyping artefact seen in patients with anti‐mouse immunoglobulin antibodies

et al. 1990

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Patients treated with murine monoclonal antibodies develop anti-mouse phocytes for immunophenotyping. immunoglobulin antibodies which can interfere with flow cytometry of lymphocytes, giving rise to high levels of nonspecific staining. This artefact can be avoided by using separated, washed lymKey terms: Cytometry, monoclonal antibodies, human immunodeficiency virus, anti-idiotypic antibodiesThe use of murine monoclonal antibodies is increasing in all fields of medicine. They are now used for in vivo diagnosis and therapy in many situations, and the development of human antibodies against both the constant and variable regions of mouse immunoglobulin has been well documented (1,2).We have been investigating the possible role of antiidiotypic antibodies against anti-CD4 monoclonal antibodies in the therapy of human immunodeficiency virus infection, the results of which will be the subject of 3 separate report. As part of the follow-up of patients immunized with six intramuscular injections of 1 mg of mti-Leu3a, a murine anti-CD4 monoclonal antibody, Ne have seen a characteristic artefact when attempting ;o enumerate T-cell subsets by flow cytometry.Flow cytometry was performed using a Becton-Dicknson FACScan cytometer, with either the Immune Monitoring Kit (IMK) panel of fluorochrome-conjugated mouse monoclonal antibodies and software, or Simulset 2-Colour antibodies and software (Bectonlickinson, San Jose, California). EDTA-anticoaguIated blood was stained and then lysed using BectonIlickinson FACS lysing solution followed by washing once in phosphate buffered saline, according to the inanufacturer's instructions. All the patients in this study have developed antibodies directed against murine immunoglobulins, demonstrable to high titre by ELISA. Coincident with the development of anti-mouse immunoglobulin antibodies, an increase in non-specific staining of up to 100% of all lymphocytes was seen, rendering immunophenotyping of lysed whole blood impossible (Fig. la,b). This characteristic artefact, which we believe is due to formation of immune complexes between the patients' anti-mouse-immunoglobulin antibodies and the monoclonal antibodies used for staining, is not due to circulating mouse Ig and it persists for a t least 6 months after immunization, in spite of considerable waning of anti-mouse Ig antibody titres as determined by ELISA. Forward and side scatter were not affected.We have found that separation of peripheral blood mononuclear cells by centrifugation over Ficoll-Paque (Pharmacia, Sweden) followed by washing the cells twice in RPMI medium is sufficient to remove this artefact and to allow immunophenotyping to be performed (Fig. lc,d).Since the therapeutic and diagnostic use of monoclonal antibodies in conditions such as HIV infection and haematological malignancies can only increase, this artefact will certainly be seen more commonly.

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Specific detection of anti-idiotypic immune responses in cancer patients treated with murine monoclonal antibody

Cited by 61 publications

References 5 publications

Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733.

Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733.

Human response against NP-4, a mouse antibody to carcinoembryonic antigen: human anti-idiotype antibodies mimic an epitope on the tumor antigen.

Characteristic immunophenotyping artefact seen in patients with anti‐mouse immunoglobulin antibodies

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