Journal of immunotherapy
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Journal of immunotherapy · Sep 2017
Review Case ReportsImmune Checkpoint Inhibitors in Organ Transplant Patients.
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant. ⋯ Although limited cases have been reported, there are circumstances in which immune checkpoint inhibitors have been used in the setting of organ transplantation without resulting in organ rejection. A thorough discussion with the patient of the potential risks, including graft rejection, and benefits of this therapy is necessary before beginning this treatment. More research is needed to explore the safety and efficacy of immune checkpoint inhibitors in the setting of organ transplantation.
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Journal of immunotherapy · May 2016
Case ReportsSuccessful Anti-PD-1 Antibody Treatment in a Metastatic Melanoma Patient With Known Severe Autoimmune Disease.
Pembrolizumab, an anti-programmed death-1 monoclonal antibody, has been approved by the Food and Drug Administration in 2014 on the basis of improved progression-free and overall survival in metastatic melanoma. We report for the first time a successful treatment with a programmed death-1 antibody in a 69-year-old metastastic melanoma patient with a Churg-Strauss lung vasculitis and a prior ipilimumab-induced autoimmune colitis. This case report suggests that pembrolizumab can be given with caution to patients with underlying autoimmune disease. As the use of checkpoint inhibitors expands, knowledge about their safety in patients with underlying autoimmune diseases will become increasingly important, in particular because these patients are typically excluded from clinical trials with immune-checkpoint inhibitors.
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Journal of immunotherapy · Nov 2012
Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-CTLA4 antibody and interferon-α or TLR-9 agonist and GM-CSF with peptide vaccination.
Changes in the biomarkers of host suppressor immune response were evaluated in patients with melanoma enrolled in 2 trials. Two similar cohorts of patients participating in the 2 studies were evaluated. The first (IFN/treme) tested interferon (IFN)-α2b and tremelimumab in metastatic melanoma and reported a response rate of 24%, 6.4 months median progression-free survival, and 21 months median overall survival. ⋯ There were no significant changes in T-reg or MDSC, except for a trend towards decreased (HLA-DR(+) low/CD14(+)) MDSC at day 50 (P = 0.07). Therefore, IFN/treme significantly downregulated MDSC suggesting a role on the significant clinical activity observed in this trial. T-reg findings suggest that IFN/treme induced clinically significant antitumor responses by inhibiting CTLA4 suppressive effects on T effectors, and less so by affecting T-reg.
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Journal of immunotherapy · Sep 2012
Induction of antitumor immunity ex vivo using dendritic cells transduced with fowl pox vector expressing MUC1, CEA, and a triad of costimulatory molecules (rF-PANVAC).
The fowl pox vector expressing the tumor-associated antigens, mucin-1 and carcinoembryonic antigen in the context of costimulatory molecules (rF-PANVAC) has shown promise as a tumor vaccine. However, vaccine-mediated expansion of suppressor T-cell populations may blunt clinical efficacy. We characterized the cellular immune response induced by ex vivo dendritic cells (DCs) transduced with (rF)-PANVAC. ⋯ Moreover, Tregs expressed high levels of Th2 cytokines [interleukin (IL)-10, IL-4, IL-5, and IL-13] together with phosphorylated STAT3 and STAT6. In contrast, the vaccine-expanded Treg population expressed high levels of Th1 cytokines IL-2 and interferon-γ and the proinflammatory receptor-related orphan receptor γt (RORγt) and IL-17A suggesting that these cells may share effector functions with conventional TH17 T cells. These data suggest that Tregs expanded by rF-PANVAC-DCs, exhibit immunosuppressive properties potentially mediated by Th2 cytokines, but simultaneous expression of Th1 and Th17-associated factors suggests a high degree of plasticity.
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Journal of immunotherapy · Jun 2012
Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors.
Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape from antitumor immunity. MDSC accumulate in the lymphoid organs and blood during tumor growth and their mobilization was also reported after cyclophosphamide (CY) administration. In this communication, spleen MDSC accumulating after CY therapy (CY-MDSC) were compared with those expanded in mice bearing human papilloma viruses 16-associated TC-1 carcinoma (TU-MDSC). ⋯ The susceptibility of CY-MDSC to all-trans-retinoic acid (ATRA) was also evaluated. In vitro cultivation with ATRA resulted in MDSC differentiation, and ATRA inhibited MDSC accumulation induced by CY administration. Our findings identified differences between CY-MDSC and TU-MDSC and supported the rationale for utilization of ATRA or IL-12 to alter MDSC accumulation after CY chemotherapy with the aim to improve its antitumor effect.