Tumor‐bound immunoglobulins. Evidence for the in vivo coating of tumor cells by potentially cytotoxic anti‐tumor antibodies

Abstract

The experiments described herein were designed to determine whether part of the Ig coat of tumor cells consists of specific anti-tumor antibodies. It was demonstrated that the inoculation of polyoma virus-induced sarcoma cells (SEYF-a) into syngeneic A.BY mice stimulates the production of cytotoxic antibodies against the tumor-cell population. The level of these antibodies, which was undetectable during the first week after transplantation, increased markedly during the second week, and remained high thereafter. Following the increase in cytotoxic antibodies in the serum, a cell-bound potentially cytotoxic antibody was detected on the tumor cells by testing their sensitivity to rabbit complement. The increase in cell-bound, potentially cytotoxic antibody followed the kinetics of the increase in serum antibody during the second week after transplantation and was inversely correlated to the amount of free antigens on the cell surface. These antigens, responsible for the sensitivity of the cells to a syngeneic hyperimmune cytotoxic antiserum, became non-available for the cytotoxic antibodies during propagation of the tumor cells. Cells from a tumor propagated for 3 weeks could not compete for anti-tumor antibodies with cells propagated for 1 week. Yet it was possible to increase the antigenic capacity of cells from an old tumor by a treatment that would cause the release of tumor-associated Ig. Cytotoxic anti-SEYF-a antibodies could be dissociated from tumor cells propagated in vivo by methods causing dissociation of antigen-antibody complexes, and detected in tumor eluates.

Tumor bound immunoglobulins: The relationship between the in vivo coating of tumor cells by potentially cytotoxic anti‐tumor antibodies, and the expression of immune complex receptors

“…The appearance of cytotoxic anti-SEYF-a antibodies in the sera of tumor-bearing mice has been previously reported (Ran et al, 1976). These antibodies were localized on in vivo propagating SEYF-a cells and occupied antigenic determinants on the cell surface.…”

“…Sensitivity of SEYF-a cells to the lytic activity of exogeneous complement correlated with propagation time in vivo. It increased during the second week of propagation time and reached peak values at the end of that week (Ran et al, 1976).…”

“…The binding of comPAOA by older tumor cell populations (19 or 20 days in vivo), was still inhibited by addition of exogenous anti-SEYF-a antibodies but to a lesser degree than the younger cell populations (about 30% as compared to 50% with 10-to 11-day-old cells). These cells, as shown above, and also previously, (Ran et al, 1976), are coated in vivo with anti-SEYF-a antibodies. However, prior removal of this in vivo surface coat by short-term incubations at 37" C completely restored the inhibition pattern to that obtained with younger (10, 11 days) tumor populations.…”

“…These antibodies were localized on in vivo propagating SEYF-a cells and occupied antigenic determinants on the cell surface. The antibodies were capable of mediating the lysis of tumor cells upon the addition of exogenous complement in vitro (Ran et al, 1976). Sensitivity of SEYF-a cells to the lytic activity of exogeneous complement correlated with propagation time in vivo.…”

Tumor-Bound Immunoglobulins

“…Perhaps, the lymphocyte and macro phage recognition system cannot distinguish between a tumor cell covered by antibodies having free antigen combining sites and normal cells, like lymphocytes, which are physiologically covered by free antibodies. The host's defense mechanism would then be incapable of recognizing the tumor cells [25], It should also be noted that many researchers found tumor-specific immunoglobulins oh the membrane of tumor cells [ 16,[26][27][28][29]. Antibody-mediated enhance ment of tumor growth [30] has suggested that these antibodies play a role in tumor propagation by mask ing antigenic determinants of tumor cells.…”