sorry, we can't preview this file

23266066cir150189-sup-153308_2_supp_3572470_pcvv2c.pptx (2.56 MB)

Supplementary Figures S3 to S6 from Tn-MUC1 DC Vaccination of Rhesus Macaques and a Phase I/II Trial in Patients with Nonmetastatic Castrate-Resistant Prostate Cancer

figure

posted on 2023-04-03, 23:07 authored by Elizabeth Scheid, Pierre Major, Alain Bergeron, Olivera J. Finn, Russell D. Salter, Robin Eady, Bader Yassine-Diab, David Favre, Yoav Peretz, Claire Landry, Sebastien Hotte, Som D. Mukherjee, Gregory A. Dekaban, Corby Fink, Paula J. Foster, Jeffery Gaudet, Jean Gariepy, Rafick-Pierre Sekaly, Louis Lacombe, Yves Fradet, Ronan Foley

Figure S3: Representative gating scheme illustrating the functional subsets induced within the memory CD4+ and CD8+ T cell pools following the stimulation of PBMCs with NP-DCs, KLH-DCs and Tn-MUC1-DCs.; Figure S4: Frequency of KLH-specific cytokine-secreting memory CD4+ T cell subsets and CD8+ T cell subsets at baseline, < 2 months, and > 6 months following vaccination.; Figure S5 Frequency of Tn-MUC1-specific cytokine-secreting memory CD4+ T cell subsets (A) and CD8+ T cell subsets (B) at baseline, < 2 months, and > 6 months following vaccination.; Figure S6: Representative gating scheme illustrating the Treg subsets induced within the CD4+ T cell pool.

History

ARTICLE ABSTRACT

MUC1 is a glycoprotein expressed on the apical surface of ductal epithelial cells. Malignant transformation results in loss of polarization and overexpression of hypoglycosylated MUC1 carrying truncated carbohydrates known as T or Tn tumor antigens. Tumor MUC1 bearing Tn carbohydrates (Tn-MUC1) represent a potential target for immunotherapy. We evaluated the Tn-MUC1 glycopeptide in a human phase I/II clinical trial for safety that followed a preclinical study of different glycosylation forms of MUC1 in rhesus macaques, whose MUC1 is highly homologous to human MUC1. Either unglycosylated rhesus macaque MUC1 peptide (rmMUC1) or Tn-rmMUC1 glycopeptide was mixed with an adjuvant or loaded on autologous dendritic cells (DC), and responses were compared. Unglycosylated rmMUC1 peptide induced negligible humoral or cellular responses compared with the Tn-rmMUC1 glycopeptide. Tn-rmMUC1 loaded on DCs induced the highest anti-rmMUC1 T-cell responses and no clinical toxicity. In the phase I/II clinical study, 17 patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC) were tested with a Tn-MUC1 glycopeptide-DC vaccine. Patients were treated with multiple intradermal and intranodal doses of autologous DCs, which were loaded with the Tn-MUC1 glycopeptide (and KLH as a positive control for immune reactivity). PSA doubling time (PSADT) improved significantly in 11 of 16 evaluable patients (P = 0.037). Immune response analyses detected significant Tn-MUC1–specific CD4+ and/or CD8+ T-cell intracellular cytokine responses in 5 out of 7 patients evaluated. In conclusion, vaccination with Tn-MUC1–loaded DCs in nmCRPC patients appears to be safe, able to induce significant T-cell responses, and have biological activity as measured by the increase in PSADT following vaccination. Cancer Immunol Res; 4(10); 881–92. ©2016 AACR.