Clinical Trial Evaluating DC/AML Fusion Cell Vaccination Alone and in Conjunction with PD-1 Blockade in AML Patients Who Achieve a Chemotherapy-Induced Remission

• Published in: Blood 2011-11, Vol.118 (21), p.948-948
• Main Authors: Rosenblatt, Jacalyn, Stone, Richard M., Avivi, Irit, Uhl, Lynne, Neuberg, Donna, Joyce, Robin, Tzachanis, Dimitrios, Levine, James D., Boussiotis, Vassiliki A, Zwicker, Jeffrey, Arnason, Jon E., Luptakova, Katarina, Steensma, David P., DeAngelo, Daniel J, Galinsky, Ilene, Vasir, Baldev, Somaiya, Poorvi, Mills, Heidi, Yuan, Yan Emily, Bonhoff, Jessica, Delaney, Carol, Drummy, Natalie, Nicholson, Lowell, Stroopinsky, Dina, Held, Vicki, Katz, Tami, Bisharat, Lina, Rowe, Jacob M., Kufe, Donald, Avigan, David
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.948.948

Abstract 948 Patients with acute myeloid leukemia (AML) achieve remission following chemotherapy; however, curative outcomes remain elusive due to relapse with chemotherapy-resistant disease. Allogeneic transplantation remains a potentially curative therapy for AML patients, but is associated with significant morbidity and mortality due to the lack of specificity of the alloreactive response. A promising area of investigation is the development of cancer vaccines that educate host immunity to more selectively target leukemia cells, including the stem cell compartment. Our group has developed a cancer vaccine model in which dendritic cells (DCs) are fused to autologous tumor cells, resulting in the presentation of multiple tumor antigens with the capacity to elicit a broad anti-tumor response. A fundamental challenge to developing a more effective tumor vaccine is overcoming the immunosuppressive milieu by which tumor cells evade host immunity. Key elements contributing to tumor-mediated immune suppression are the increased presence of regulatory T cells in patients with malignancy, and upregulation of the PD-1/PDL1 pathway. Tumor expression of PD-L1 promotes T cell tolerance by binding PD-1 on activated T cells and suppressing their capacity to secrete stimulatory cytokines. In addition, the PD-1/PDL-1 pathway has been shown to inhibit T cell-mediated lysis of tumor cells, potentially preventing a clinically meaningful immunologic response to vaccination. We are conducting a clinical trial in which AML patients who are in a first or second complete remission following chemotherapy receive three monthly doses of DC/AML fusion cells alone (Cohort 1) or in conjunction with anti-PD1 antibody, CT-011 (cohort 2). To date, 16 patients (9 males, 7 females; mean age 55 years) have been enrolled to the first cohort. All patients underwent successful tumor collection from either a bone marrow aspirate (N=12), collection of 20 cc of peripheral blood (N=3), or leukapheresis product (N=1) at the time of presentation with newly diagnosed AML (N=15) or first relapsed AML (N=1). The mean yield was 1.45×108 cells, and the mean viability was 90%. Tumor cells were subjected to immunohistochemical analysis to identify antigens unique to the leukemia fusion partner. Those patients achieving complete remission following 1–2 cycles of induction chemotherapy underwent leukapheresis for dendritic cell generation. Adherent peripheral blood mononuclear cells were isolated, cultured i