The goal of the proposed study is to assess the immunogenicity of a vaccine comprising autologous tumor cells plus GM-CSF-in-adjuvant, followed by systemic low-dose IL-2, in patients with resected high-risk melanoma. We have found that vaccination with GM-CSF-in-adjuvant is effective at generating immune responses to defined peptide antigens in human subjects. Autologous tumor cell vaccines may have advantages over vaccination with defined tumor antigens because (1) some patients' tumors do not express the tumor-associated antigens that have been identified, (2) some patients are not eligible for peptide-based trials because they do not have the correct human leukocyte antigen (HLA) type, and (3) there may be less chance of tumor escape from immune surveillance as a result of antigen loss. On the other hand, whole cell vaccines are complicated by (1) the complexity of the antigen mixture, (2) poor understanding of the ideal environment for presentation of cell-derived antigens, (3) the lack of standardization, and (4) the possibility that tumor-cell-derived factors may inhibit immune responses. The clinical study proposed here is a pilot study that will seek preliminary evidence (a) that a vaccine comprising autologous tumor cells plus GM-CSF-in-adjuvant, followed by low-dose IL-2 therapy, will result in increased autologous tumor-reactive immunity in high risk melanoma patients, (b) that tumor-reactive immunity measured in vaccinated patients will include T-cell responses against defined melanoma peptides as well as responses against unique antigens, (c) that evaluation of lymph nodes draining the immunization site will permit a more sensitive assessment of the immunogenicity of the vaccine than evaluation of peripheral blood, and (d) that GMCSF-in-adjuvant administered locally, as a component of an autologous tumor cell vaccine, will induce changes in T-cell activation markers in the lymph node draining the vaccination site. We anticipate that results derived from this study will yield important preliminary data regarding T-cell responses in melanoma patients receiving this type of immunotherapy. These data will then provide a foundation for subsequent rigorous evaluation of a whole cell vaccine versus vaccination with purified defined antigens.
| Deacon, Donna H; Hogan, Kevin T; Swanson, Erin M et al. (2008) The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines. BMC Cancer 8:360 |
| Slingluff Jr, Craig L; Chianese-Bullock, Kimberly A; Bullock, Timothy N J et al. (2006) Immunity to melanoma antigens: from self-tolerance to immunotherapy. Adv Immunol 90:243-95 |
| Chianese-Bullock, Kimberly A; Woodson, Elizabeth M H; Tao, Huimin et al. (2005) Autoimmune toxicities associated with the administration of antitumor vaccines and low-dose interleukin-2. J Immunother 28:412-9 |
