1988; Fontana, Frei et al. 1989). Recently, however, several advances have been made with respect to mechanisms by which the immune system can actually be manipulated to facilitate tumor antigen recognition and enhance anticancer immune effector activity in cancer. Two independent approaches involving gene-based vaccines, specifically, Belagenpumatucel-L and GVAX ®, have demonstrated, in Mary Crowley Cancer Research Centers and other institutional studies, remarkable safety and significant benefit with respec t to response and survival benefits in advanced cancer patients (Nemunaitis ; Eager, Harle et al. 2007; Nemunaitis and Nemunaitis 2007; Murray N 2010). Mo reover, enhancement of tumor antigen recognition following treatment was correlated with patient benefit. Protocol # CL-PTL 105 CONFIDENTIAL AM #9 09/25/15 Page 12 Immune Function Capacity in Cancer Patients 1.2 Tumor cells often continue to express normal cellular antigens in addition to neo- antigens that are recognized by the i mmune system of the tumor-bearing host. The production of tumor specific antibod ies by B cells can be elicited by the immunization of animals with tumor ce lls, and tumor-asso ciated determinants have been defined by their ability to stimulate an antibody response in association with their presence on tumor cells. Detectable titers of antibodies that bind to tumor-associated anti gens have been demonstrated in cancer patients, but there is no compelling evidence that administration of exogenous antibodies to tumor-associated determinant s cause solid tumors to regress in humans. However, there is an accumulating body of evidence to suggest that many tumors in experimental model syst ems and from cancer patients express molecules that are targeted by t he T cell arm of the immune system. Rejection of antigen-expressing tumor cells has been shown to be mediated by specific host cytolytic T cells (Prien RT 1957; Kripke 1974). Tumor infiltrating lymphocytes, or TIL, have been shown to mediate durable regression of established tumors in mice with adv anced tumor burdens (Yang, Perry-Lalley et al. 1990; Barth RJ 1991). In patients bear ing metastatic tumors, a number of groups have demonstrated the existence of anti-tumor CTL responses. Peripheral blood mononuclear cells as well as TIL contain populations of cells and individual clones that demonstrate tumor specificit y; they lyse autologous tumor cells, but not natural killer target s, allogeneic tumors cells, or autologous fibroblasts (Anichini, Mazzocchi et al. 1989; Darrow, Slingluff et al.