Activation of MHCRestricted T Cells

Pre-clinical research, particularly in murine models, has identified four conceptually distinct strategies for inducing T cells capable to destroy tumors in vivo through MHC-restricted recognition by ab+ T-cell receptors expressed by the majority of T cells. They include the following:

1. Administration of systemic or locally injected im-munostimulants to tumor-bearing animals to effectively expand already activated endogenous tumor-reactive T cells.

2. In vivo administration of a tumor vaccine, either purified or crude/complex, containing antigenic components of the tumor itself, designed to induce and expand endogenous tumor-reactive T cells to mediate tumor selective destruction.

3. In vitro activation, selection, manipulation, and/or expansion to generate a population of tumor-reactive autologous T cells able to mediate anti-tumor destruction in vivo upon adoptive transfer.

4. Infusion of allogeneic T cells, either directly obtained ex vivo, or potentially modified in vitro, to induce a "graft-vs-tumor" response which takes advantage of genetic or physiological differences between the tumor-bearing host and the healthy allogeneic lymphocyte donor.

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