The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily

Heath, Joan K.; White, Sara J.; Johnstone, Cameron N.; Catimel, Bruno; Simpson, Richard J.; Moritz, Robert L.; Tu, Guo Fen; Ji, Hong; Whitehead, Robert H.; Groenen, Leo C.; Scott, Andrew M.; Ritter, Gerd; Cohen, Lawrence E.; Welt, Sydney; Old, Lloyd J.; Nice, Edouard C.; Burgess, Antony W.

doi:10.1073/pnas.94.2.469

Cited by 161 publications

(98 citation statements)

References 36 publications

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“…This rate is in competition with other rates including the clearance of the secondary agent from the body (k clearance ) and internalization of the antibody (k endocytocis ). cancer LS174Tcell line (22). In addition, this antigen is associated with tight junction proteins, giving it a surface persistence with a half life greater than 2 d (23).…”

Section: Resultsmentioning

confidence: 99%

Reactive polymer enables efficient in vivo bioorthogonal chemistry

Devaraj

Thurber

Keliher

et al. 2012

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

171

187

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There has been intense interest in the development of selective bioorthogonal reactions or "click" chemistry that can proceed in live animals. Until now however, most reactions still require vast surpluses of reactants because of steep temporal and spatial concentration gradients. Using computational modeling and design of pharmacokinetically optimized reactants, we have developed a predictable method for efficient in vivo click reactions. Specifically, we show that polymer modified tetrazines (PMT) are a key enabler for in vivo bioorthogonal chemistry based on the very fast and catalyst-free [4 þ 2] tetrazine/trans-cyclooctene cycloaddition. Using fluorescent PMT for cellular resolution and 18 F labeled PMT for whole animal imaging, we show that cancer cell epitopes can be easily reacted in vivo. This generic strategy should help guide the design of future chemistries and find widespread use for different in vivo bioorthogonal applications, particularly in the biomedical sciences.in vivo chemistry | pharmacokinetics | PET imaging | intravital microscopy | pretargeting T he ability to perform selective chemistries in living systems such as single cells, 3D cultures, invertebrates, or mammals would have far reaching applications in tracking biomolecules, designing new therapeutic approaches, and in visualizing medically relevant biomarkers. To date, only a few practical bioorthogonal reactions have been reported, the most popular being the Staudinger ligation and the [3 þ 2] cycloaddition "click" reaction between azides and alkynes (1, 2). The latter click reaction involves copper(I) catalyzed coupling of an azide and terminal alkyne to generate a stable triazole (2). Until recently, the necessity of the copper catalyst precluded use of this reaction in biological systems due to toxicity concerns (3, 4). Bertozzi and others elegantly solved this problem by developing several new ring strained dienophile derivatives that do not require catalysts (5-9). However, many of these derivatives have low water solubility, require complex multistep synthesis, and possess suboptimal kinetics. Our search for alternative rapid, selective, and chemically accessible coupling reactions without need for a catalyst led us and others to investigate the [4 þ 2] inverse Diels-Alder cycloaddition (10-13). We realized that this set of chemistries is more uniquely suited to biological applications and may indeed represent a universal platform technology ( Fig. 1 A and B). Specifically we and others have shown that the cycloaddition between tetrazine (Tz) and trans-cyclooctene (TCO) can proceed orders of magnitude faster than previously studied azide and alkyne click reactions and importantly does not require the action of a catalyst. This reaction has also been adapted for single cell imaging using newer fluorogenic Tz probes (14).Although initial work focused on in vitro labeling there has been a surge of recent work applying this reaction for various in vivo applications (15-17). Despite the above progress, our results with initial TCO...

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Section: Resultsmentioning

confidence: 99%

Reactive polymer enables efficient in vivo bioorthogonal chemistry

Devaraj

Thurber

Keliher

et al. 2012

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

171

187

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“…The antigen target is a critical element in the success of this approach, and one of the most promising targets in colorectal cancer is the A33 antigen: a novel glycoprotein with a molecular weight of 43 kDa, with homology to the immunoglobulin superfamily (10 -12). A33 consists of two extracellular immunoglobulin domains, a single transmembrane domain, and a short intracellular tail containing four acylation sites proximal to the transmembrane domain (11,12). Extensive immunohistochemical analysis of malignant and normal tissues has shown that the antigen is homogeneously expressed by >95% of colon cancers and in the normal intestinal mucosa but not in other epithelial tissues (13,14).…”

mentioning

confidence: 99%

A Phase I Trial of Humanized Monoclonal Antibody A33 in Patients with Colorectal Carcinoma: Biodistribution, Pharmacokinetics, and Quantitative Tumor Uptake

Scott

Lee

Jones³

et al. 2005

Clinical Cancer Research

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111

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“…The A33 antigen is a cell surface glycoprotein present only in the small intestine and colonic epithelium with homology to proteins of the immunoglobulin superfamily, such as the coxsackievirus and adenovirus receptor (19). In human cancer, A33 was found in 95% of primary and metastatic colorectal carcinomas, 63% of diffuse gastric cancers, 83% of intestinaltype gastric cancers, 50% of pancreatic cancers, and f50% of the diffuse-type and mucinous cancers; it was absent in epithelial cancers, sarcomas, neuroectodermal tumors, and lymphoid neoplasms (20,21).…”

mentioning

confidence: 99%

A Novel A33 Promoter–Based Conditionally Replicative Adenovirus Suppresses Tumor Growth and Eradicates Hepatic Metastases in Human Colon Cancer Models

Cafferata

Macció

López

et al. 2009

Clinical Cancer Research

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Purpose: A33 antigen is a membrane-bound protein expressed in intestinal epithelium that is overexpressed in 95% of primary and metastatic colorectal carcinomas but is absent in most epithelial tissues and tumor types. We hypothesized that A33 promoter might be useful in the design of a conditionally replicative adenovirus for the treatment of colorectal cancer (CRC). Experimental Design: We cloned an A33 promoter fragment (A33Pr) that extends from -105 to +307 bp. Using luciferase activity as a reporter gene, we showed that A33Pr was active in CRC cell lines. We next constructed a conditionally replicative adenovirus named AV22EL where E1A was placed under the control of A33Pr. The tumor-specific oncolytic effect of AV22EL was investigated both in vitro and in vivo. Results: AV22EL induced specific in vitro lysis of human CRC cell lines that expressed A33 and have negligible lytic capacity on cells that lacked or had minimal A33 expression, including normal human colonic cells. In vivo, a marked reduction of tumor growth and increased long-term survival rates were observed in nude mice xenografted with s.c. CRC tumors. Combination with 5-fluorouracil induced an additive effect in vitro with no toxic effects in vivo. Remarkably, AV22EL completely eliminated established hepatic metastases in >90% of mice and restored hepatic function according to biochemical parameters. Its systemic administration induced E1A expression only in the hepatic metastasis but not in normal organs. Conclusions: These data show that AV22EL is a stringently regulated and potent oncolytic agent for the treatment of CRC.Colorectal cancer (CRC) is the second most common cause of cancer mortality in Western countries and claimed >50,000 lives a year only in the United States. 4 Close to 70% of patients that are affected by colorectal carcinoma undergo surgical resection and 30% to 40% of them develop a recurrent disease (1). The liver is the most common site of metastatic CRC and complete resection of hepatic metastases is the only curative option; however, surgery can be done only in 20% of patients at the time of diagnosis and 5-year survival rates average 25% to 40% despite adjuvant chemotherapy (2). Among patients with metastatic colorectal carcinoma receiving as first-line chemotherapy 5-fluorouracil (5-FU) and new medications, such as irinotecan, Xeloda, oxaliplatin, Erbitux, and Avastin, the median time to progression is 8 to 9 months and their mean survival is 15 to 20.5 months (3 -6). It seems therefore that current CRC treatments are rather ineffective on advanced disease, showing the need for more effective and specific therapeutics to significantly increase patients' survival.Conditionally replicative oncolytic adenoviruses (CRAd) have shown promising applications in cancer gene therapy (7,8). One strategy to achieve specific elimination of the tumor mass, avoiding negative undesired effects in contiguous normal tissue, is the use of tumor-selective transcriptional regulation to control the essential early E1 genes, whic...

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The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily

Cited by 161 publications

References 36 publications

Reactive polymer enables efficient in vivo bioorthogonal chemistry

Reactive polymer enables efficient in vivo bioorthogonal chemistry

A Phase I Trial of Humanized Monoclonal Antibody A33 in Patients with Colorectal Carcinoma: Biodistribution, Pharmacokinetics, and Quantitative Tumor Uptake

A Novel A33 Promoter–Based Conditionally Replicative Adenovirus Suppresses Tumor Growth and Eradicates Hepatic Metastases in Human Colon Cancer Models

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