Upon encountering an antigen, naïve CD4+ T-helper precursor cells enact a process that results in differentiation toward either a T-helper type 1 (Th1) or T-helper type 2 (Th2) lineage.  Th1 cells produce IL-2 and IFN-  and mediate Type 1 immunity, whereas Th2 cells produce IL-4, IL-5, and IL-10 [20] and mediate Type 2 immunity.  Th1 and Th2 immune responses are counter-regulatory, such that increased Type 1 responses downregulate Type 2 responses and increased Type 2 responses downregulate Type 1 responses [21].  Type 1 immunity has been shown to be critical for immune-mediated protection against tumors as well as tumor eradication [22-24],  Tumor-mediated deviation of CD4 differentiation to Th2 and Type 2 immunity  is a tumor strategy for immunoavoidance and survival [25].

A therapeutic cancer vaccine must be able to elicit the de-novo development of a Type 1 response that overwhelms and disables the resident Type 2 response to a tumor.  This can be accomplished by controlling the microenvironment in which tumor antigens are presented to the immune system. The presence of Type 1 or Type 2 cytokines can drive uncommitted T cells to develop a cytokine profile similar to the one to which they are exposed, while at the same time inhibiting the development of cells with the reciprocal phenotype. Thus, IFN-γ, a Type 1 cytokine, selectively expands Th1 cells and inhibits proliferation of Th2 cells, while IL-4 and IL-10, Type 2 cytokines, can selectively inhibit cytokine secretion by Th1 cells [26].  

From these concepts it can be concluded that Type 1 cytokines are a required component of a therapeutic cancer vaccine.  AlloStim™ cells are differentiated in culture to produce large amounts of Type 1 cytokines.  Because AlloStim™ cells are recognized as foreign by the host immune system, they will be rejected.  Since these foreign cells produce large amounts of Type 1 cytokines, they are expected to steer the immune response to their foreign antigens to Th1.  In this manner, the rejection process is expected to serve to increase the number of circulating Th1 memory immune cells in the circulation of patients injected with the experimental drug.