TY - JOUR
T1 - Tumor infiltrating lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma
T2 - Interim findings from the INSPIRE trial
AU - Wolf, Gregory T.
AU - Liu, Siyu
AU - Bellile, Emily
AU - Sartor, Maureen
AU - Rozek, Laura
AU - Thomas, Dafydd
AU - Nguyen, Ariane
AU - Zarins, Katie
AU - McHugh, Jonathan B.
AU - Moyer, Jeff
AU - Patel, Mihir
AU - Saba, Nabil
AU - Erman, Audrey
AU - Martins, Wanessa A.
AU - Newman, Jason G.
AU - Kaplan, Michael
AU - Oliveira, Frabicio
AU - Paula Victorina, Ana
AU - Bryan Bell, R.
AU - Girotto, Gustavo C.
AU - Nieva, Jorge
AU - Valentino, Joseph
AU - Krempl, Greg
AU - Cernea, Claudio R.
AU - Kraus, Dennis
AU - Higgins, Kevin
AU - Cruz, Felipe J.S.M.
AU - Panwar, Aru
AU - Campos, Clodoaldo Z.
AU - McCaul, Jim
N1 - Publisher Copyright:
© 2020
PY - 2020/12
Y1 - 2020/12
N2 - Objectives: IRX-2 is a primary-cell-derived immune-restorative consisting of multiple human cytokines that act to overcome tumor-mediated immunosuppression and provide an in vivo tumor vaccination to increase tumor infiltrating lymphocytes (TILs). A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery consisting of an initial dose of cyclophosphamide followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2). Methods: A total of 96 patients with previously untreated, stage II-IV oral cavity SCC were randomized 2:1 to experimental (1) or control (2) regimens (64:32). Paired biopsy and resection specimens from 62 patients were available for creation of tissue microarray (n = 39), and multiplex immunohistology (n = 54). Increases in CD8+ TIL infiltrate scores of at least 10 cells/mm2 were used to characterize immune responders (IR). Results: Regimen 1 was associated with significant increases in CD8+ infiltrates (p = 0.01) compared to Regimen 2. In p16 negative cancers (n = 26), significant increases in CD8+ and overall TILs were evident in Regimen 1 (p = 0.004, and 0.04 respectively). IRs were more frequent in Regimen 1 (74% vs 31%, p = 0.01). Multiplex immunohistology for PD-L1 expression confirmed an increase in PD-L1 H score for Regimen 1 compared to Regimen 2 (p = 0.11). Conclusions: The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT 02609386).
AB - Objectives: IRX-2 is a primary-cell-derived immune-restorative consisting of multiple human cytokines that act to overcome tumor-mediated immunosuppression and provide an in vivo tumor vaccination to increase tumor infiltrating lymphocytes (TILs). A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery consisting of an initial dose of cyclophosphamide followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2). Methods: A total of 96 patients with previously untreated, stage II-IV oral cavity SCC were randomized 2:1 to experimental (1) or control (2) regimens (64:32). Paired biopsy and resection specimens from 62 patients were available for creation of tissue microarray (n = 39), and multiplex immunohistology (n = 54). Increases in CD8+ TIL infiltrate scores of at least 10 cells/mm2 were used to characterize immune responders (IR). Results: Regimen 1 was associated with significant increases in CD8+ infiltrates (p = 0.01) compared to Regimen 2. In p16 negative cancers (n = 26), significant increases in CD8+ and overall TILs were evident in Regimen 1 (p = 0.004, and 0.04 respectively). IRs were more frequent in Regimen 1 (74% vs 31%, p = 0.01). Multiplex immunohistology for PD-L1 expression confirmed an increase in PD-L1 H score for Regimen 1 compared to Regimen 2 (p = 0.11). Conclusions: The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT 02609386).
KW - Immunotherapy
KW - Neoadjuvant
KW - Oral cavity carcinoma
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U2 - 10.1016/j.oraloncology.2020.104928
DO - 10.1016/j.oraloncology.2020.104928
M3 - Article
C2 - 32738599
AN - SCOPUS:85089531228
SN - 1368-8375
VL - 111
JO - Oral Oncology
JF - Oral Oncology
M1 - 104928
ER -