Sera from mice carrying progressively growing sarcomas induced by Moloney virus or methylcholanthrene can block the cytotoxic effect of lymphocytes immune to the tumor-specific antigens of the respective neoplasms. The blocking effect can be specifically removed by absorbing sera with the respective types of tumor cells, and it can be recovered from these cells by elution at low pH. If the low pH is maintained, it is possible to separate out a low and a high molecular weight fraction from the eluates. If the fractions are added to the target cells for 45 minutes and then removed, neither of these fractions can block lymphocyte-mediated cytotoxicity, while a 1:1 mixture of them has a specific blocking effect. If they are admixed with the lymphocytes, incubated for 1 hr, and then allowed to incubate with the target cells and lymphocytes during the entire 2 days of the test, the low molecular weight fraction, as well as the mixture, but not the high molecular weight fraction, has a blocking activity.It is suggested that the blocking factor in sera from tumor-bearing animals, as regularly tested, is an antigenantibody complex, capable of binding to the target cells and/or reacting with lymphocytes immune to their antigens, thus blocking the lymphocytes' reactivity; the latter reaction is postulated to be of a temporary nature.Lymph-node cells and circulating blood lymphocytes from tumor-bearing animals and human patients have a specific cytotoxic effect on cultivated tumor cells from the same individuals (1-5). The cytotoxicity is almost the same as with lymphocytes obtained after the tumors have been removed.Progressive tumor growth in vivo, despite a strong cellmediated anti-tumor immunity demonstrable in vitro, has been attributed to a specific ability of the serum of tumorbearing individuals to prevent target cell destruction by immune lymphocytes (2, 6-12); the mechanisms of the protection may be similar to those of the in vivo phenomenon of immunological enhancement (13). Sera from tumor-bearing animals, but not from tumor-free ones, can also abrogate the migration inhibition seen when peritoneal cell suspensions from specifically immune donors are exposed to tumor-antigen extracts in vitro (14).The specificity of the blocking-serum activity suggests that it might be antibody-mediated. This conclusion is also supported by the findings that the blocking activity can be specifically removed by absorption of sera with tumor cells of the respective types (2), that the blocking fraction of the serum has the gel filtration characteristics of 7S immunoglobulin (2,15), and that the blocking activity can be removed by incubation with antiserum to immunoglobulin (2).One may hypothesize that blocking antibodies bind to the target tumor cells and thereby mask their antigens from detection by immune lymphocytes. Alternatively, one may visualize the blocking factors as antigen-antibody complexes, capable of acting on the target cells, the lymphocytes, or both, any action on the lymphocytes having to be of a temporar...

Sera from patients with growing neoplasms have been previously shown capable of specifically blocking the cytotoxic effect of lymphocytes immune to tumor-associated antigens ( T A A ) of the respective patients' neoplasms. The present investigation demonstrates that a similar blocking activity can be eluted at pH 3.1 from human tumor tissues, obtained at surgery (seminomas and osteogenic sarcomas) and from tumor cells growing in ascites and pleural effusions (carcinomas of endometrium, breast and ovary). A high ( M W above 100,000) and a low ( M W below 100,000) molecular weight fraction can be separated from the eluates by ultrafiltration. Neither of these fractions could block lymphocyte-mediated cytotoxicity in vitro when tested by itself, while a I:I mixture of them could. Blocking was also obtained when the tumor cells were first exposed to the high and then to the low molecular weight fractions, but not when the sequence was reversed. The observations obtained are analogous to previous findings in animal tumor systems and provide evidence that tumors growing in human patients are coated by '' blocking factors ".Most human neoplasms have tumor-associated antigens (TAA) capable of inducing immunity in their hosts (Klein, 1971;Hellstrom and Hellstrom, 1972;Morton et al., 1968). This immunity