Cancer Prevention by Adoptive Transfer of Antigen 60‐Activated Immunocompetent Cells

Abstract

The authors have already shown that A60, the thermostable macromolecular antigen complex of Mycobacterium bovis BCG, induced resistance to tumour challenge in several murine systems. In the present work, the authors provided evidence that activated macrophages played a major role, and cytolytic T lymphocytes a minor one, in both in vivo and in vitro A60-promoted cancer cell cytolysis. To identify the types of immunocompetent cells involved in this protective effect, macrophages and T lymphocytes from A60-primed mice donors were adoptively transferred to irradiated recipients prior to EMT 6 tumour challenge. In some groups, A60-primed donors were survivors of previous tumour challenges. Transfer of T lymphocytes from the spleen or lymph-nodes of A60-immunized mice induced 80-90% protection against tumour challenge. Conversely, transferred macrophages, although cytolytically active, did not induce resistance to tumour implantation. Furthermore, adoptive transfer with T lymphocytes from A60-immunized and EMT 6 challenge-surviving donors induced 100% protection. It is concluded that stimulation of T lymphocytes by A60 is the key step which leads to activation of the immunocompetent cells involved in tumour rejection.

Immunological relatedness of the protective mechanisms against tuberculosis and cancer

“…All the specific functions of activated MΦ, be it tumour cytolysis or production of oxygen and nitrogen radicals, were reduced in MΦ confronted with cancer cells. However, in agreement with the cited adoptive transfer experiments (inability of MΦ alone to protect irradiated hosts against tumour challenge; Table 2) [ 79], TLs from A60‐primed mice, after pre‐incubation with EMT 6 tumour cells in vitro , displayed a reduced ability to activate Mφ ( Fig. 6C) [ 80].…”

“…Irradiated reference mice, receiving EMT 6 cells and lymphocytes from naive mice, develop lethal tumours within 1 month. In contrast, irradiated mice injected with activated lymphocytes from A60‐primed mice, but not those receiving MΦ alone, are protected against a subsequent tumour challenge [ 79]. It is thus evident that MΦ, although the main effectors of tumour cytolysis, need a continuous activation by stimulated specific lymphocytes.…”

“…The demonstration that anti‐tuberculous immunity is transferred by blood cells and not by serum [ 17–19] bears a strong similarity with the adoptive transfer of A60‐activated competent cells for protection against tumour challenge ( Table 2) [ 79].…”