Human cancers express organ-specific cancer neoantigens (OSN) as determined by in vitro leukocyte responses to extracts of cancers by the tumor host. In this study, we determined whether the OSNs were normal developmental proteins that were expressed by fetal organs and re-expressed with oncogenesis. Fetal extracts, principally of lung and colon but also of liver and kidney, were tested for their ability to induce leukocyte adherence inhibition (LAI) as compared to extracts from adult tissues of the same organ. Leukocytes from lung cancer patients showed positive LAI responses to 13- and 19-week fetal lung tissue. Likewise, leukocytes from colon cancer patients showed positive LAI responses to 14- and 19-week fetal colon tissue, whereas leukocytes from control subjects did not. Neither group responded positively to 21-week fetal organs. Criss-cross experiments showed that the fetal antigen was organ specific. Multiparous pregnant women showed positive LAI responses to cancer extracts but not to extracts from normal tissues of the same organ. The pattern of the LAI response was bell-shaped. Positive LAI responses to lung and breast cancer were detected at 4 to 7 months gestation and peaked at 5 months. To the fetal colon, LAI positive responses were detected at 5 to 8 months gestation, with the peak response at 6 months. The results indicate that OSN of cancers are also expressed by fetal organs and sufficient antigen is shed by fetal organs to sensitize pregnant women. Older fetal organs (21 weeks) and adult organs do not express an immunogenic or antigenic OSN.

The antitumor immune response of monocytes armed with cytophilic antitumor antibody to an organ-specific neoantigen of human bladder cancer was measured by the tube leukocyte adherence inhibition assay. Of 29 patients with Stage A bladder cancer, 27 had positive tests, whereas of 11 patients with Stage B, C and D bladder cancer, 2 had positive tests. If the leukocytes from advanced bladder cancer patients were preincubated briefly with prostaglandin E2, the negative response was converted to positive. Of 189 patients with diseases of other organs, 2 had positive tests. Patients with acute or chronic cystitis had negative tests. The sensitivity of the assay was 88 per cent; specificity was 95 per cent. The bladder cancer extracts prepared from metastatic tissue or the tissue-cultured cell line, T24, had similar activity in the assay. Normal bladder tissue did not share the bladder cancer organ-specific neoantigen nor did cancers of other organs. Bladder epithelial cells expressed the OSN before they acquired invasive properties since patients with dysplastic bladder epithelium or in-situ cancer had positive tests. Antitumor immunity was often detectable before a recurrence became obvious by cystoscopy or cytology of urine and became undetectable quickly after removal of the bladder cancer. Of 100 patients with prior bladder cancer without evidence of exophytic tumor, 18 had positive tests; the possibility must be considered seriously that some had precancerous changes which formed no visible gross abnormalities. The results suggested that antitumor immunity to bladder cancer was a sensitive indicator of precancerous or cancerous changes existing in epithelial cells.