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Serologic Evaluation Using Monoclonal and Polyclonal Antibodies — Their Diagnostic and Prognostic Usefulness
Published in John T. Kemshead, Pediatric Tumors: Immunological and Molecular Markers, 2020
Differentiation antigens are cytoplasmic- or membrane-associated sites on normal adult tissue or on neoplastic cells from which they have been derived, i.e., neuron specific enolase. Oncofetal antigens are restricted to normal fetal cells and also can be expressed on tumor cells, i.e., carcinoembryonic antigen or alpha fetoprotein. Proliferation antigens are present in small amounts on normal epithelium and are strongly expressed by proliferating cells (transferrin receptor). These categorical descriptions will be helpful in understanding the individual markers in the sections below.
Antigenic Status of Trophoblast in Humans and Mice
Published in Gérard Chaouat, The Immunology of the Fetus, 2020
As the name implies, an oncofetal antigen is defined by its presence only on certain fetal and malignant tissues. Unfortunately, similar to most definitions, this is an oversimplification because several antigens included in this group also show limited expression on some adult tissues.31 Many tissue-restricted trophoblast antigens can be included. The search for oncofetal and “tissue-specific” trophoblast membrane antigens has been more productive than that for minor histocompatibility antigens, which are usually ubiquitous, although some also show tissue specificity.26
Oncogenes and Cancer
Published in Pimentel Enrique, Oncogenes, 2020
The increased levels of oncogene products could correspond, at least in some cases, to a general phenomenon of dedifferentiation or retrodifferentiation occurring in the tumor cells. Thus, it may be similar to the re-expression of oncofetal antigens and other biochemical changes occurring in many types of human tumors, as well as in tissue and organ regenerative processes. The molecular mechanisms involved in the regulation of oncofetal antigen expression are apparently not specific for these antigens but may include regulation of other unlinked and unrelated structural genes.104 Furthermore, the general physiological conditions of the patient and the local conditions of the tumor tissue may have influence on the expression of genes present in the tumor cells, including the proto-oncogenes. However, the genes encoding oncofetal antigens and other proteins expressed in tumor cells have not apparent transforming ability and it seems likely that particular proto-oncogenes participate, in conjunction with other cellular genes, in the complex, multistage processes related to tumorigenesis, which are associated with many fold changes in the expression of different genomic functions. In particular, proto-oncogenes may contribute to the biochemical phenomena associated with progression of certain tumors. The possible role of active proto-oncogenes in the production of metastasis is suggested by the fact that a metastatic phenotype is expressed in cells transfected with DNA extracted from human metastatic tumors.105
Current strategies for the discovery and bioconjugation of smaller, targetable drug conjugates tailored for solid tumor therapy
Published in Expert Opinion on Drug Discovery, 2021
Mahendra P. Deonarain, Gokhan Yahioglu
The advantages of antibody fragments over whole monoclonal antibodies, like rapid tumor accumulation and enhanced penetration are negated by their rapid overall clearance. PEGylation and half-life extension technologies like albumin-binding domains (ABD) are commonly used to alter and improve the PK profile of many biological proteins. This was clearly demonstrated with a diabody targeting the oncofetal antigen 5T4, where ABD fusion or conjugation of two PEG20K chains altered the half-life of the diabody from minutes to days [52]. A similar study was carried out with the diabody conjugated to a PBD warhead (DAR 2). This was either carried out with maleimide terminated payload at engineered cysteines on the ABD-diabody fusion or on dual-functionalized a 5T4 azido-diabody with the alkyne functionalized PBD drug linker followed by site-specific PEGylation at the engineered cysteines (Figure 1(f)). In an in vivo efficacy study, a clear link between PK and antitumour activity was observed with the ABD-diabody-PBD showing the best tumor growth suppression and tolerability compared to the PEG-diabody-PBD and diabody-PBD [52].
Diagnostic work-up in paediatric and adolescent patients with adnexal masses: an evidence-based approach
Published in Journal of Obstetrics and Gynaecology, 2021
Milan Terzic, Agnese Maria Chiara Rapisarda, Luigi Della Corte, Rahul Manchanda, Gulzhanat Aimagambetova, Melanie Norton, Simone Garzon, Gaetano Riemma, Cara Robinson King, Benito Chiofalo, Antonio Cianci
Tumour markers, as a term, generally refer to developmentally regulated proteins that are expressed in or derived from neoplastic tissues. Cancer biomarkers are biomolecules produced either by the tumour cells directly or by other cells of the body in response to the tumour (Terzic et al. 2014). They can be used in screening/early detection tool of cancer, diagnostics, prognostics, or as predictors for the overall outcome of a patient. Moreover, a specific subpopulation of patients may be identified by cancer biomarkers (i.e. genes, gene products, specific cells, molecules, enzymes, or hormones), which can be detected in blood, urine, tissues, or other body fluids, in order to understand who most likely is capable of responding to a given therapy. Traditionally, cancer biomarkers are made up of proteins or carbohydrate molecules, which are expressed in the foetus during the developmental period; thus, these were also known as ‘oncofetal antigens’. An ideal tumour marker is a molecule released by the tumour cells in quantities easily detectable in the circulation or body fluids of the host proportionally to the tumour burden and absent in the non-tumour bearing hosts (Terzić and Dotlić 2016).
Exosomes from GM-CSF expressing embryonic stem cells are an effective prophylactic vaccine for cancer prevention
Published in OncoImmunology, 2019
Kavitha Yaddanapudi, Shuhan Meng, Aaron G. Whitt, Numan Al Rayyan, Jamaal Richie, Allison Tu, John W. Eaton, Chi Li
A popular hypothesis of tumorigenesis suggests that mutations in undifferentiated progenitor cells give rise to malignant cells that are capable of both self-renewal and differentiation. Interestingly, this theory essentially predicted the discovery of cancer-initiating cells (CICs) that came over 100 years later. In an example of history repeating itself, in the mid-1960s, tumor cells and embryonic stem cells were shown to possess common gene products such as the oncofetal antigens. During the ensuing decade, a large number of studies confirmed these findings and revealed that embryonic antigens are re-expressed in cells from solid tumors from a number of different tissues and that vaccination of animals with fetal material can prevent the outgrowth of tumors (see review)1. It now appears that most, if not all, types of neoplastic cells express certain embryonal antigens; this phenomenon has been termed “retrogenetic expression”.2 Many of these embryonic gene products (also called carcinoembryonic antigens) are not expressed in the adults and thus, are not included in the repertoire of ‘self’ during the process of thymic selection that occurs near the end of gestation. Such ‘non-self’ embryonic antigens are immunogenic and can prime the immune cells to mount an anti-tumor response.3 Exploiting such embryonic antigen immunogenicity, we have designed a unique stem cell-based vaccine that stimulates the immune system to recognize shared oncofetal antigens and confers protection against tumors.