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Immune function of epithelial cells
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Richard S. Blumberg, Wayne Lencer, Arthur Kaser, Jerrold R. Turner
However, in contrast to professional APCs, epithelial cells lack the expression of the classical costimulatory molecules CD80 and CD86 but do express novel members of the B7 family, including inducible costimulatory ligand (ICOS) and programmed death-1 ligand (B7-H1). Further molecules that are relevant for epithelial cell–lymphoid cross talk and are constitutively expressed on epithelial cells are leukocyte function-associated antigen-3 (LFA-3; CD58), E-cadherin, the IL-7 receptor (IL-7R), carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1), and CEACAM5 (CEA), as well as the common γ chain, which is required for signaling through the IL-2R, IL-4R, IL-7R, IL-9R, and IL-15R. CD86 may be expressed on epithelial cells during the inflammation associated with inflammatory bowel disease.
Radioimmunodetection of Cancer: The Next Dimension
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
David M. Goldenberg, Robert M. Sharkey
The first monoclonal antibody imaging agent to receive the FDA approval (1992) was satumomab pendetide (Onco-Scint) for imaging of colorectal cancer metastases and then later also for detection of ovarian cancer metastases (42–49). This is an intact IgG murine mAb against TAG-72 glycoprotein that is elaborated by a number of carcinomas and labeled with 111In. Because IgG clears slowly from the blood, images were delayed several days to secure optimal tumor-background uptake ratios. More important to the diagnostic utility of this agent was the fact that because IgG is catabolized by the liver and because 111In is retained inside the cells, the normal liver contained a higher level of 111In activity than tumor, which meant that liver metastases would usually appear as negative lesions against a hot liver background. In 1996, arcitumomab (CEA-Scan) was also approved for use in conjunction with CT to identify colorectal cancer metastases. This agent was an IgG-Fab’ against CEA (CEACAM5), which is expressed by a majority of carcinomas, and labeled with 99mTc. Since an IgG-Fab’ clears more rapidly from the blood than an IgG, visualization was possible within a few hours, with 24-hour imaging feasible for verification. It clears from the body primarily through renal/urinary clearance, and thus liver metastases could be seen as hot lesions (except if they are very large, interfering with mAb penetration) (40). However, increased uptake by the kidneys and in the urine excreted into the bladder often required SPECT to disclose lesions in these regions. An intact IgG mAb against prostate-specific membrane antigen, labeled with 111In, was approved in 1996 for imaging prostatic carcinoma patients suspected of having lymph node metastases presurgically and also in those suspected in having a postsurgical recurrence (50–57). In this case, the IgG form is preferred because there is less activity in the urinary bladder, an anatomic region of interest for prostate cancer. This product, capromab pendetide (ProstaScint), is still in commercial use in the United States. In 1997, the FDA also approved a 99mTc-labeled anti-EGP1 (epithelial glycoprotein-1) mAb Fab’ (nofetumomab or Verluma) for staging of small cell lung cancer (58). Except for the prostate cancer-imaging agent, the others have been removed from the market.
Molecular Nodal Restaging Based on CEACAM5, FGFR2b and PTPN11 Expression Adds No Relevant Clinical Information in Resected Non-Small Cell Lung Cancer
Published in Journal of Investigative Surgery, 2022
Ivan Macia, Gemma Aiza, Ricard Ramos, Ignacio Escobar, Francisco Rivas, Anna Ureña, Samantha Aso, Gabriela Rosado, Pau Rodriguez-Taboada, Carlos Deniz, Ernest Nadal, Gabriel Capella
In our setting the lack of added value of the molecular staging seems directly related to the observed better clinical outcome of primary tumors overexpressing CEACAM5 and FGFR2b. Of note, there are not many studies that evaluate the prognostic impact of tumor overexpression of CEACAM5. CEACAM5 is a well-known tumor marker and the increased serum levels have been associated with a worse evolution [26]. Okayama et al. reported a trend toward poor outcome in cases overexpressing CEACAM5 [27]. PTPN11 overexpression is also associated with a slight better prognosis. There is no straightforward explanation for this observation as PTPN11, a member of the PDL1 (programmed cell death 1 ligand 1)-PD1 (programmed cell death 1) cascade, inhibits immune response [28]. In all, the potential value of nodal restaging may be strongly related to biological behavior of the tumors harboring the tested molecular marker.
Extensive genomic analysis in patients with KRAS-mutated solid tumors shows high frequencies of concurrent alterations and potential targets but has limited clinical impact
Published in Acta Oncologica, 2022
Ida Christine Jacobsen, Iben Spanggaard, Martin Højgaard, Laïla Belcaid, Camilla Qvortrup, Christina Westmose Yde, Ane Yde Schmidt, Finn Cilius Nielsen, Gro Linno Willemoe, Mikkel Seidelin Dam, Ulrik Lassen, Kristoffer Staal Rohrberg
Mutations in the tumor suppressor genes APC and TP53 are frequent alterations in human cancers [27,28], but cannot yet be targeted with therapy. High expression of CEACAM5 was considered an actionable target as several trials with bispecific antibodies targeting CEACAM5 were accruing patients with high CEACAM5 expression at our facility during the study period. HRD, TMB high, loss of PTEN, pathogenic mutations in FBXW7, PIK3CA, ATM, BRAF (V600E), ERBB3, and IDH1, and amplifications of ERBB2, EGFR, CDK4, MDM2, and MET were also considered actionable, all of which were found in this study, with ESCAT levels ranging from I-A to IV (Supplementary Table 5).
Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin
Published in OncoImmunology, 2019
Raquel Ibáñez-Pérez, Patricia Guerrero-Ochoa, Sameer Al-Wasaby, Rocío Navarro, Antonio Tapia-Galisteo, Diego De Miguel, Oscar Gonzalo, Blanca Conde, Luis Martínez-Lostao, Ramón Hurtado-Guerrero, Laura Sanz, Alberto Anel
The carcinoembryonic antigen (CEA), also known as CEACAM5,23 was originally described in colorectal cancer (CRC)24 as one of the first ever identified tumor-associated antigens, although its expression at lower levels has been reported in normal tissues. The heterogenous CEACAM (CEA-related cell adhesion molecule) family belongs to the immunoglobulin superfamily and comprises 12 genes in humans, at least three of them expressed in epithelia: CEACAM1, CEACAM5 and CEACAM6.25,26 The functions attributed to CEA family members are very diverse and include modulation of tumor growth, metastasis, innate and adaptive immunity, angiogenesis, and host–microbial interaction.25–27 CEA is a GPI anchored molecule released by proteolytic and non-proteolytic mechanisms.28 In fact, serum levels of CEA are useful in predicting prognosis and monitoring response to treatment in CRC.29 Of note, the antitumoral effect of CEA-targeted therapies is not inhibited by soluble CEA, as assessed with bispecific anti-CEA x anti-CD3 antibodies30 and CAR T cells containing an anti-CEA scFv as targeting domain.31 MFE23 is a scFv produced by phage display technology that binds to CEA with high affinity and has distinct tumor targeting advantages.32–34 Recently, a trimerbody based on the MFE23 scFv has been produced with high yield and activity in the yeast P. pastoris.35 Although cross-reactivity of MFE23 with other CEACAM family molecules bearing similar N-terminal domains (such as CEACAM1 and CEACAM6) has not been addressed, their similar expression pattern may preclude recognition of non-targeted tissues.