Graft-Versus-Tumor (GvT) Effects in the Absence of Alloantigens on Tumor Cells Crucially Depend on Graft-Versus-Host Disease (GvHD) Intensity.

While a variety of tumors is potentially immunogenic and is capable to trigger tumor-associated antigen (TAA)-specific immune responses in vivo the endogenous immune system usually fails to eradicate established tumors. Despite considerable effort and promising experimental and preliminary clinical data most cellular immunotherapeutic strategies have not evolved into a clinically relevant treatment strategy with allogeneic immune replacement as cancer immunotherapy being the sole exception. At this juncture allogeneic HSCT not only allows for otherwise fatal high-dose chemo- and radiotherapy intended to reduce the tumor cell burden but also encompasses potent immunologically mediated anti-tumor effects, referred to as GvT reaction. This GvT reaction, which is based on donor T and natural killer cells, is interrelated, however, with potentially deleterious GvHD, one of the major limitations of allogeneic HSCT. Mutated tumor-associated antigens, as well as selectively or aberrantly expressed nonmutated antigens, represent potential targets for T cell-mediated GvT effects that are in principle, separable from generalized anti-host responses. Using an allogeneic parent-into-F1 murine transplantation model (BALB/c or C57BL/6 → [C57BL/6 x BALB/c]F1) with different chemically induced tumors derived from either parental strain, we have previously demonstrated that a significant CD8+ T cell-mediated GvT effect accounts for immunological tumor control after allogeneic HSCT in vivo. Remarkably, this effect occurs in the absence of histoincompatibilities between donor immune cells and host tumor (