Its efficacy is rooted in a phenomenon known as “the allogeneic effect”.4, 9 T lymphocytes have the ability to recognize a very broad range of foreign proteins (antigens), but, at least initially, only a very tiny fraction of lymphocytes can recognize a given antigen.
However, a relatively high proportion of lymphocytes are pre-programmed to recognize the so-called “histocompatibility antigens” (derived from HLA proteins) that are different than those on one’s own cells. When a patient receives an organ transplant from a donor that has not been carefully matched, many his lymphocytes quickly recognize the foreign histocompatibility antigens expressed by the transplanted organ; this results in rapid rejection of the organ if strong immunosuppressive drugs are not administered concurrently.
This marked tendency of T lymphocytes to recognize and react to foreign histocompatibility antigens is known as “alloreactivity”. The lymphocytes infused in Dr. Kondo’s therapy are said to be “allogeneic” because they express different histocompatibility antigens than the patient, and thus recognize the patient’s histocompatibility antigens as foreign.
Dr. Ephraim Fuchs and colleagues of Johns Hopkins Medical School have recently demonstrated, working with tumor-bearing rodents, how the phenomenon of alloreactivity can be employed to generate a strong anti-cancer immune response.
Direct attack of tumor cells by the infused lymphocytes (known as a “graft-versus-host response”) plays little if any role in the efficacy of this strategy. Rather, the major efficacy reflects the fact that infused T helper lymphocytes (bearing the marker CD4+) are capable of greatly boosting the activity of the patient’s “antigen-presenting cells” (dendrites), because a high proportion of these infused helper lymphocytes can recognize the histocompatibility antigens expressed by these dendrites.
If these stimulated antigen-presenting cells have assimilated tumor proteins that can be perceived as foreign by the host’s immune cells, they then have the capacity to confer strong activation to the patient’s own cytotoxic T lymphocytes (bearing the marker CD8+) that can recognize these tumor proteins.
These stimulated cytotoxic T lymphocytes can then directly attack and kill the cancer cells. This strategy is more effective because the preliminary chemotherapy has selectively eliminated many of the suppressor lymphocytes which otherwise could have limited the activation or activity of these tumor-directed cytotoxic T lymphocytes.
Dendrites activated by infused alloreactivity lymphocytes can also markedly enhance the activity of natural killer cells, immune cells which can recognize and attack many cancer cells in a way that is not dependent on the recognition of specific tumor antigens.
At Oasis, we use Dr. Kondo’s classic allogeneic lymphocyte therapy in the context of other measures which can boost the efficacy of the anti-cancer immune response, either by amplifying the activation of the cytotoxic T lymphocytes and natural killer cells capable of attacking the cancer, or by blocking strategies which tumors often employ to ward off immune rejection.
These measures include melatonin, subcutaneous injections of interleukin-2 (employed with the CMIT-IL regimen), high-dose selenium (which Dr. Kondo also used!), spirulina, glutamine, the cox-2 inhibitor diclofenac, and caffeine.