Tumor infiltrating lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma: Interim findings from the INSPIRE trial

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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).

Original languageEnglish
Article number104928
JournalOral Oncology
StatePublished - Dec 2020

Bibliographical note

Funding Information:
This work was supported in part by grant funding from Brooklyn ImmunoTherapeutics, Inc., Brooklyn, New York; Clinical trial sponsorship by Brooklyn Immunotherapeutics, Inc. and the Rogel Cancer Center, University of Michigan, Ann Arbor, MI and National Cancer Institute of the NIH under award number P30 CA046592.

Funding Information:
Dr. Wolf was recipient of grant funding from the clinical trial sponsor, Brooklyn ImmunoTherapeutics, for central laboratory tissue collection and correlative immune studies.

Publisher Copyright:
© 2020


  • Immunotherapy
  • Neoadjuvant
  • Oral cavity carcinoma

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


Dive into the research topics of 'Tumor infiltrating lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma: Interim findings from the INSPIRE trial'. Together they form a unique fingerprint.

Cite this