Adenovirus tumor-specific transplantation antigen is a function of the E1A early region.

Abstract

Viable recombinant adenoviruses that carry a portion of the type 12 E1A and E1B transcription units in a type 5 background were used to identify genes controlling expression of the adenovirus tumor-specific transplantation antigen (TSTA). The TSTA immunity is not crossreacting between the group A and group C adenovirus serotypes. Viruses carrying the E1A region (sub370-12E1A), or both E1A and E1B (sub370-12E1AB) regions of Ad12, induce a strong transplantation immunity against tumors induced by syngeneic cells transformed with adenovirus 12, but fail to induce any protection against syngeneic cells transformed with adenovirus 2. Immunization with the virus carrying only the E1B region (sub370-12E1B) of adenovirus 12 induces no immunity to adenovirus 12 transformed cell line, but confers a strong protection against cells transformed with adenovirus 2. These results provide strong evidence that the adenovirus tumor-specific transplantation antigen is a function of the E1A early region.

Tumorigenic adenovirus 12 cells evade NK cell lysis by reducing the expression of NKG2D ligands

“…E1A and E1B, the first viral products synthesized after virus entry, are entirely responsible for the transformation phenotype; however, only E1A encoded by tumorigenic adenoviruses can promote tumorigenesis. Ad12 E1A renders the host cell less immunogenic by manipulating pathways involved in regulating both the innate and adaptive immune responses [2,3]. This supported by the fact that non-tumorigenic adenovirus serotypes are capable of forming tumors in immunosuppressed rodents [4,5].…”

Identification of functional domains of adenovirus tumor‐specific transplantation antigen in types 5 and 12 by viable viruses carrying chimeric E1A genes

“…This line induces tumors in syngeneic animals with high efficiency and short latency period. It has been used as a standard for quantitation of inducton of Ad-group-C TSTA immunity in rats (Gallimore and Williams, 1982;Sawada et al, 1986). The EcoC3 cell line was transformed with a recombinant plasmid containing the EcoRI-C fragment (0-16.5 map units) of Ad12 DNA and serves for monitoring of induction of Ad 12 syngraft immunity (Sawada et al, 1986).…”

“…It has been used as a standard for quantitation of inducton of Ad-group-C TSTA immunity in rats (Gallimore and Williams, 1982;Sawada et al, 1986). The EcoC3 cell line was transformed with a recombinant plasmid containing the EcoRI-C fragment (0-16.5 map units) of Ad12 DNA and serves for monitoring of induction of Ad 12 syngraft immunity (Sawada et al, 1986). For tumorigenicity assays, the 2 cell lines were passaged in animals and subsequently not more than 6 times in tissue culture.…”

“…The use of welldefined Ad mutants offers a tool for such investigation. The fact that transplantation immunity against Ad tumors and Ad-specific CTL are highly specific and are not cross-reacting between group-A and group-C serotypes has made it possible to establish that Ad TSTA and Ad-specific CTL recognition targets are products coded for by the Ad E1A oncogene (Sawada et al, 1986;Urbanelli et al, 1989).…”

“…Products of these CRs show about 50% homology between different Ad groups. This homology is sufficient for conservation of E1A functional activities, yet there is no cross-reactivity in transplant immunity between group-A and group-C adenoviruses (Sawada et al, 1986;Gallimore and Williams, 1982). Utilization of deletion mutants of Ad5 have made it possible to map the TSTA function and cytolytic T-cell (CTL) target structures of the Ad group C in the rat model to the 3' exon of the E1A oncogene (Urbanelli et al, 1989).…”