On the nature of cancer and why anticancer vaccines don't work

Abstract

In this essay I suggest that the major difficulty in producing effective anti-cancer vaccines lies in the fact that most cancers have little immunogenicity because of a basic paucity of tumor-specific antigenicity. The lack of antigenicity, despite extensive genomic instability, could be explained if most tumor mutations occur in silenced genes. A further problem is that an immune reaction against tumor antigens, especially in moderate or low amount, may be stimulatory rather than inhibitory to tumor growth.It is now almost half a century since the overthrow of Ehrlich's doctrine of "horror autotoxicus" and the general acceptance of the contrary idea that animals can indeed be immunized against the growth of a transplanted syngeneic cancer. Why then is it that, despite nearly 50 years of intense investigation, attempts to use the immune reaction as a tool against cancer have, with the exception of bladder cancer, met with only moderate success? What is the realistic prospect that the next 50 years will see an improvement in this dismal state of affairs? Many investigators, myself included, have a large vested interest in the field of cancer immunology and will be reluctant to entertain any discouraging viewpoint, but the actual facts are, I believe, discouraging.

Tumor reductive therapies and antitumor immunity

“…With sensitive assays and the precise knowledge of antigens, we saw that modern tumor vaccines did activate specific immune responses in patients [ 47 , 48 ]. However, the lack of significant overall clinical efficacy triggered tumor immunologists to question this approach [ 49 , 50 ]. Yet, the belief that the immune system has the power to eradicate cancer was sustained due to occasional outliers of extreme efficacy.…”