Limited Improvement of Tumour Diagnosis by the Simultaneous Determination of Carcinoembryonic Antigen (CEA) and of a Tumour-Associated CEA-Related Antigen of Mr 128000 in Serum

Wagener, Christoph; Wickert, Lucia; Meyers, Wayne M.

doi:10.1515/cclm.1989.27.9.643

Cited by 3 publications

(2 citation statements)

References 27 publications

(29 reference statements)

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“…Mapping antibody reactivity with this antigen is therefore of interest, even if the clinical relevance (if any) is still not known [31]. Five MAbs with A3B3 reactivity reacted poorly with meconium CEA, clearly demonstrating that the two forms of the CEA gene product are different.…”

Section: Discussionmentioning

confidence: 99%

Protein Epitopes in Carcinoembryonic Antigen

Bjerner¹,

Lebedin²,

Bellanger³

et al. 2002

Tumor Biol

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To characterize antigenic sites in carcinoembryonic antigen (CEA) further and to investigate whether there are differences between colon tumor CEA and meconium CEA (NCA-2) that can be detected by anti-CEA monoclonal antibodies (MAb), 19 new anti-CEA MAb were analyzed with respect to specificity, epitope reactivity and affinity. Their reactivities were compared with 10 anti-CEA MAb with known CEA-domain binding specificity that have previously been classified into five nonoverlapping epitope groups, GOLD 1–5. Cross-inhibition assays with antigen-coated microtiter plates and immunoradiometric assays were performed in almost all combinations of MAbs, using conventionally purified CEA (domain structure: N-A1B1-A2B2-A3B3-C) from liver metastasis of colorectal carcinomas, recombinant CEA, meconium CEA (NCA-2), truncated forms of CEA and NCA (CEACAM6) as the antigens. The affinity of the MAbs for CEA was also determined. The new MAbs were generally of high affinity and suitable for immunoassays. Three new MAbs were assigned to GOLD epitope group 5 (N-domain binding), 3 MAbs to group 4 (A1B1 domain), 1 to group 3 (A3B3 domain), 3 to group 2 (A2B2 domain) and 3 to group 1 (also the A3B3 domain). Three MAbs formed a separate group related to group 4, they were classified as GOLD 4′ (A1B1 domain binding). The remaining 3 MAbs appear to represent new subspecificities with some relationship to GOLD groups 1, 2 or 4, respectively. Five MAbs, all belonging to epitope group 1 and 3, reacted strongly with tumor CEA but only weakly or not at all with meconium CEA, demonstrating that the two products of the CEA gene differ from each other, probably due to different posttranslational modifications.

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Section: Discussionmentioning

confidence: 99%

Protein Epitopes in Carcinoembryonic Antigen

Bjerner¹,

Lebedin²,

Bellanger³

et al. 2002

Tumor Biol

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“…As a result, elevated CEA levels can often be detected in the serum of cancer patients (22). CEA assays have been used to address questions related to diagnosis, staging, monitoring, and prognosis of carcinomas with variable success (23,24). Postsurgical monitoring of colon cancer by CEA assays is now generally accepted as a useful and cost-effective tool (25).…”

mentioning

confidence: 99%

A carcinoembryonic antigen‐specific diabody produced in tobacco

et al. 2002

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The feasibility of using tobacco for production of a recombinant antibody (T84.66/GS8 diabody) directed against the carcinoembryonic antigen (CEA) and used for tumor imaging was investigated. Two constructs were generated for targeting the protein either to the apoplast or to the endoplasmic reticulum. Expression of the diabody in tobacco leaves after vacuum-assisted infiltration of engineered Agrobacteria (agro-infiltration) and in regenerated transgenic tobacco plants was analyzed and compared. Results in terms of protein expression and accumulation between both systems showed a good correlation. His6-tagged T84.66 diabody was readily purified from agro-infiltrated tobacco leaves and from transgenic plants by immobilized metal ion affinity chromatography. The purified protein was analyzed by polyacrylamide gel electrophoresis, Western blot, gel filtration, electrospray mass spectrometry, direct and competition ELISA, electrophoretic mobility shift assay, and staining of CEA-positive colon adenocarcinoma cell line LS174T. Our results demonstrate that tobacco is a competent production system for this clinically relevant diabody.

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An optimal antitumor response by a novel CEA/CD3 bispecific antibody for colorectal cancers

Wang¹,

Patel²,

Schneider

et al. 2021

Antibody Therapeutics

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Background CD3-based bispecific T cell engagers (bsTCEs) are one of the most promising bispecific antibodies for effective cancer treatments. To elicit target-specific T cell-mediated cytotoxicity, these bsTCEs contain at least one binding unit directed against a tumor antigen and another binding unit targeting CD3 in T cell antigen receptor complex. Development of CD3-based bsTCEs, however, has been severely hampered by dose limiting toxicities due to cytokine release syndrome. To address this limitation, we developed a novel functionally trivalent TCE (t-TCE) antibody containing affinity reduced CD3 binding unit, positioned to ensure monovalent CD3 engagement, in combination with bivalent tumor antigen binding of Carcinoembryonic Antigen (CEA). Methods We modeled the variable region of anti-CD3 in the CDRs of the heavy chain and obtained CD3 binders with reduced binding affinity. Two optimized versions CEA/CD3-v1 and CEA/CD3-v2 were identified and generated in tetravalent format, characterized and compared in vitro and in vivo. Results Our lead candidate, CEA/CD3-v2, demonstrated sub-nanomolar binding and picomolar potency against a panel of CEA-expressing cancer cell lines. In addition, we detected reduced T cell cytokine release with potent cytotoxic activity. Our t-TCE CEA/CD3-v2 molecule demonstrated strong anti-tumor effect in a dose dependent manner in human PBMC xenograft model. Furthermore, combination of CEA/CD3-v2 with atezolizumab provided synergistic antitumor effect. Conclusions Because of effective tumor cell killing with various level of CEA expression and reduced cytokine release, CEA/CD3 BsTCE may greatly benefit in CEA positive cancer immunotherapy. Statement of Significance. Through optimization of CD3 binding affinity and tetravalent format with functional monovalent binding to CD3, t-TCE CEA/CD3–2 molecule not only retains high potency in vitro and in vivo, but also significantly reduces cytokine release.

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Limited Improvement of Tumour Diagnosis by the Simultaneous Determination of Carcinoembryonic Antigen (CEA) and of a Tumour-Associated CEA-Related Antigen of Mr 128000 in Serum

Cited by 3 publications

References 27 publications

Protein Epitopes in Carcinoembryonic Antigen

Protein Epitopes in Carcinoembryonic Antigen

A carcinoembryonic antigen‐specific diabody produced in tobacco

An optimal antitumor response by a novel CEA/CD3 bispecific antibody for colorectal cancers

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