H. Tegtmeyer

Anti-N reagents in elucidation of the genetical basis of human blood-group MN specificities.

Abstract. Studies of the reactivity of the various anti‐human blood group N reagents with isolated human blood group M and N antigens and smaller molecules revealed besides the expected interaction with N antigens that M antigens inhibited all rabbit anti‐N sera, Vicia graminea extract and most human anti‐N sera. Mild acid hydrolysis of M antigens, which released sialic acid only, led to a large increase or de novo appearance of this inhibitory capacity. The partially hydrolyzed M antigens became temporarily indistinguishable from N antigens, indicating that the product of the N gene is the immediate precursor of the product of the M gene and that the allele to the M gene is an amorph. In the NM biosynthetic pathway, the Vicia‐reactive structure seems to precede the N‐specific molecule.

Origin of anti-Thomsen-Friedenreich (T) and Tn agglutinins in man and in White Leghorn chicks.

Summary. Interest in anti‐Thomsen‐Friedenreich (T) antibodies has increased because of their significance in detection of and their possible interaction with human adenocarcinoma. The origin of anti‐T, which all humans possess, has not been ascertained. We determined here that anti‐T and ‐Tn agglutinins could readily be induced via the physiological intestinal route by an enteric bacterium, E. coli O86, which possesses T and Tn activities.

Tn, a carcinoma-associated antigen, reacts with anti-Tn of normal human sera

Tn antigen is the immediate precursor of the carcinoma (CA)‐associated T antigen; both are masked in non‐CA tissues. Tn antigen was detected by absorption of human anti‐Tn antibody in 46 of 50 primary breast CAs and in all 6 metastases originating from Tn‐positive primary CAs. Thirteen of 25 (52%) anaplastic CAs, but only 2 of 15 (13%) well differentiated CAs had more Tn than T; 1 anaplastic CA had neither antigen. Eighteen of 20 benign breast lesions had no Tn; the 2 positive lesions were premalignant. All 19 breast CAs, studied immunohistochemically, reacted strongly with human polyclonal anti‐Tn; benign or normal glandular tissues had minimal or no reactivity. Among live cancer cell lines, the most malignant sublines had more Tn than T on their cell surfaces. Preliminary studies with rodent monoclonal anti‐Tn and anti‐T antibodies gave immunohistochemical reactivity patterns similar to those of the polyclonal antibodies, but the former were less sensitive in absorption tests. Tn is a CA marker that promises to be useful in tumor detection.

Monoclonal Antibodies Specific for Human Thomsen-Friedenreich (T) and Tn Blood Group Precursor Antigens

Abstract We have prepared rat x rat hybrid myelomas producing monoclonal antibodies specific for blood group precursor T and Tn haptens. We used standard procedures and fused spleen cells from DA rats, immunised with desialylated human erythrocytes, with Y3 rat myeloma cells. Anti-T and -Tn specificities were proven by agglutination, absorption, elution and inhibition assays. Histochemical studies using the immunoperoxidase procedure showed the antibodies to react specifically with carcinoma cells.

Human blood groups M-, N-, T-, and Tn-specific substances in lipidic extracts of line 10 hepatocarcinoma of Strain 2 guinea pigs

Live line 10 (L-10) hepatocarcinoma cells of Strain 2 guinea pigs carry immunoreactive human blood group T (Thomsen-Friedenreich)- and Tn-specificities on their surface as determined with human antisera. Disintegrated L-10 cells show in addition M and N activities; this indicates their presence within the tumor cells. Blood groups S and D(Rh0) activities were not demonstrable. M and N but not Tn and T specificities were also found in normal submaxillary and sublingual glands, kidney, and liver of Strain 2 guinea pigs. After extraction of L-10 carcinoma cells with n-butanol-water, all activities resided in the organic phase. Extraction of the organic phase by Sevags deproteinization procedure yielded nearly eight times as much active material (by weight) in the chloroform layer as in the aqueous layer. Depending on the antisera used, M and N activities of the extracts amounted to 10 to >100% of authentic red cell M and N glycoproteins, Tn activity to ∼75%, and T activity to between 5 and 10% of that of human red blood cell-derived T antigen. The active extracts had <0.75% protein and <3.50% ash. We report two novel findings: (a) the occurrence of M and N specificities in nonprimates, and (b) the association of these specificities with lipidic substances.

Murine lymphoma cells possess blood group Tn-, T-, N-, M- and S-active substances

Tand Tn blood group antigens are clinically important because transformation of ordinary epithelium to carcinoma (CA) in man is linked in ca. 95% of the cases with exposure of one or the other, but most commonly both of these ordinarily masked antigens on the outer surface of the CA cell membrane. T antigen also occurs on human T cell lymphomas (LPH). Tand Tnspecific structures are conserved in all metastases (tested up to > 6 y after removal of primary CA) [1-5]. These structures, accessible to the immune system, generally are not found in any other diseased nor in healthy human tissues, including fetal [2, 6, 7]. The patient recognizes his CAor LPH-associated T antigen as foreign and responds immunologically to it in a readily measurable way [2, 4, 5, 9-12]. Tnand T-specific cell surface structures may be advantageous for malignant cells as indicated by the universal occurrence of these antigens on CAs and their conservation throughout the metastatic process, not only in man but also in animals, where they are found on glycoproteins and glycolipids [2, 13]. The patients immune response against Tn and T should, in general, be detrimental rather than helpful to tumors. To assess the possibility of a supportive role of Tnand T antigens in the malignant process we studied the Eb and ESb lines of the murine methylcholanthrene-induced DBA/2-derived T LPH L5178Y; the Eb LPH has low metastatic potential and, in vitro, it does not adhere to isolated syngeneic hepatocytes, whereas the ESb line derived from Eb is highly metastatic and ESb cells form rosettes with isolated syngeneic hepatocytes in vitro [14, 15].

Delayed-type cutaneous hypersensitivity to Thomsen-Friedenreich (T) antigen in patients with pancreatic cancer☆

The delayed-type hypersensitivity skin reaction to human erythrocyte-derived Thomsen-Friedenreich (T) antigen was studied in 40 patients with pancreatic disease and in 158 control subjects and its sensitivity and specificity were compared with the carcinoembryonic antigen (CEA) blood levels. The skin reaction to T was positive in 22 of 25 patients with biopsy-proven adenocarcinoma of the pancreas (sensitivity, 88%). In these patients, the CEA levels were elevated above 3.5 ng/ml in 12 of 23 (52%). The skin test to T antigen was negative in 11 of 12 patients with chronic pancreatitis (specificity, 92%), but CEA levels were normal in only five of nine with pancreatitis (56%). Two of the patients with pancreatic carcinoma and one of those with pancreatitis were anergic to mumps and dermatophytin antigens and had thus an invalid skin test. The positive response rate to T antigen was significantly greater (P less than 0.005) in the cancer group than the group with pancreatitis; the CEA response was not significantly different. There were no positive responses to T in 82 healthy volunteers. Among 76 patients with chronic disease including six with malignant tumors of the mesoderm and central nervous system, there were four positive responses: two in heavy smokers and two in patients with chronic lung infection. The specificity of the test overall in 158 controls was thus 97.5%.

Patients mount an autoimmune response to their bladder cancer-associated T antigen

1. Cotton, F.A., Walton, R.A.: Multiple Bonds between Metal Atoms. New York: Wiley Interscience 1982 2. Robinson, E.A.: J. Chem. Soc. Dalton Trans. 1981, 2373 (siehe dort weitere Lit.) 3. Cotton, F.A., Hall, W.T.: Inorg. Chem. I9, 2352 (1980) 4. Cotton, F.A., Hall, W.T. : ibid. 19, 2354 (1980) 5. Hey, E., et al. : Z. anorg, allg. Chem. (im Druck) 6. Howard, J.A.K., Stansfield, R.F.D., Woodward, P.: J. Chem. Soc. Dalton Trans. 1976, 246 7. Uhl, G., et al. : Z. anorg, allg. Chem. (im Druck) 8. Kristalldaten von [NbCla(C6Hs-CC-C6Hs)]4:Raumgruppe P[, Z=2 dimere Einheiten NbC13(C6Hs C =-C C6H5), a= 1074,3(4), b = 1389,6(5), c = 1299,4(6) pm, c~ = 104,28(3) ~ t = 107,99(4) ~ y= 108,72(3) ~ 1548 unabh/ingige, beobachtete Reflexe, R = 5,9%

Absence of B Antibody in a Blood Group A1 Person1

Abstract. A healthy Caucasian woman who possessed blood groups A2H(O) on her red cells as well as in her saliva and serum had no anti‐blood group B ‘complete’ or ‘incomplete’ agglutinins nor hemolysins as determined either on whole serum or its concentrated β‐γ‐globulin fraction. No anti‐B antibody was stimulated by immunization with highly active human blood group B glycoprotein.

TN, A General Carcinoma-Associated Antigen

Abstract Tn antigen, the immediate precursor in the biosynthesis of T (Thomsen-Friedenreich) antigen does not occur in immunoreactive form in healthy tissues. However, we found it in about 90% of all primary carcinomas (CAs) and their metastases, as well as in the two T lymphomas studied. Thus, Tn is a CA-associated antigen. All humans possess “naturally occurring” antibodies against Tn.