76 research outputs found
Teneurins: Role in Cancer and Potential Role as Diagnostic Biomarkers and Targets for Therapy
Teneurins have been identified in vertebrates as four different genes (TENM1-4), coding for membrane proteins that are mainly involved in embryonic and neuronal development. Genetic studies have correlated them with various diseases, including developmental problems, neurological disorders and congenital general anosmia. There is some evidence to suggest their possible involvement in cancer initiation and progression, and drug resistance. Indeed, mutations, chromosomal alterations and the deregulation of teneurins expression have been associated with several tumor types and patient survival. However, the role of teneurins in cancer-related regulatory networks is not fully understood, as both a tumor-suppressor role and pro-tumoral functions have been proposed, depending on tumor histotype. Here, we summarize and discuss the literature data on teneurins expression and their potential role in different tumor types, while highlighting the possibility of using teneurins as novel molecular diagnostic and prognostic biomarkers and as targets for cancer treatments, such as immunotherapy, in some tumors
DNA vaccines against ErbB2+ Carcinomas: From mice to humans.
DNA vaccination exploits a relatively simple and flexible technique to generate
an immune response against microbial and tumor-associated antigens (TAAs). Its
effectiveness is enhanced by the application of an electrical shock in the area of plasmid
injection (electroporation). In our studies we exploited a sophisticated electroporation
device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is
an additional factor that dramatically modulates the efficacy of a vaccine, we selected
ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell
membrane by several carcinomas for which it plays an essential role in driving their
progression. Most oncoantigens are self-tolerated molecules. To circumvent immune
tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human
ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant
for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In
several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than
plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to
blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2+ carcinomas of the oral cavity,
oropharynx and hypopharynx is awaiting the approval of the Italian authorities
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