Suggestive Evidence That the “Blocking Antibodies” of Tumor-Bearing Individuals May Be Antigen-Antibody Complexes

TLDR

The blocking factor in sera from tumor‑bearing animals is proposed to be an antigen‑antibody complex that binds target cells or reacts with antigen‑specific lymphocytes, temporarily inhibiting their cytotoxicity. The blocking activity is removed by absorbing sera with tumor cells and can be recovered by low‑pH elution, which separates the activity into low‑ and high‑molecular‑weight fractions. Sera from tumor‑bearing mice block lymphocyte cytotoxicity; the low‑molecular‑weight fraction alone or mixed with the high‑molecular‑weight fraction blocks activity when incubated with lymphocytes, whereas the high‑molecular‑weight fraction alone does not.

Abstract

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 antigen-antibody 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.