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

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Abstract
The adenovirus (Ad) EIA gene induces in immunized animals a strong tumor transplantation (TSTA) immunity against Ad tumors. Such immunity with group‐A and group‐C viruses is highly group‐specific and no cross‐protection is detected between se retypes 5 and 12. This fact was used to map the domains of the Ad 5 and Ad12 EIA gene products, respectively, which control the TSTA. We constructed a library of 8 recombinant viruses (H5sub1101 through H5sub1108) which carry chimeric Ad5/Ad12 EIA genes in the background of Ad5. The chimeric genes are functional and these viruses are viable. Some of these constructs induce strong and highly specific tumor syngraft immunity in immunized rats. The viruses carrying the 5′ terminus of the first EIA exon derived from Ad12 (viruses H5sub1101, H5sub1102 and H5sub1103) induce strong protection against Ad12 tumors irrespective of the rest of their EIA sequence. The viruses which carry the second exon of the AdS EIA gene (viruses H5sub1101, H5sub1102 and H5sub1106) protect against group‐C tumors, regardless of the origin of the rest of their EIA gene. The 2 viruses that carry the 5′ EIA terminus of the first exon of Ad12 and the second exon of AdS (H5sub1101 and H5sub1102) are thus effective in inducing immunity against Ad12 tumors as well as against Ad2 tumors. The viruses which carry the 5′ terminus of the first exon derived from Ad5 and the second exon of Ad12 (H5sub1107 and H5sub1108) fail to induce immunity against either tumor. Expression of only the truncated 5′ terminus of the Ad12 EIA gene (viruses H5sub1104 and H5sub 1105) is sufficient for induction of Ad12 TSTA. Our results provide direct and unequivocal in vivo evidence that TSTA activities of adenovirus groups A and C are controlled by different domains of their respective EIA genes. The Ad12 TSTA is a function of the 5′ terminus of the first EIA exon, while the Ad5 TSTA is coded for by the 3′ exon of its EIA gene.