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Poster display session

3874 - Immune profile analysis of head and neck squamous cell carcinoma before and after neoadjuvant treatment with the IRX-2 regimen

Date

10 Sep 2017

Session

Poster display session

Topics

Cytotoxic Therapy;  Cancers in Adolescents and Young Adults (AYA);  Translational Research;  Head and Neck Cancers

Presenters

Gregory Wolf

Citation

Annals of Oncology (2017) 28 (suppl_5): v372-v394. 10.1093/annonc/mdx374

Authors

G.T. Wolf1, J.G. Newman2, N.L. Berinstein3, M.J. McNamara4, A. Nguyen1, J.E. Egan5, M.J. Kaplan6

Author affiliations

  • 1 Otolaryngology-head And Neck Surgery, University of Michigan, 48109-5942 - Ann Arbor/US
  • 2 Otolaryngology, U of Penn, Philadelphia/US
  • 3 Medical Oncology, Sunnybrook Health Sciences Center, Toronto/CA
  • 4 Chiles Research Institute, Providence Portland Medical Center, Portland/US
  • 5 Reearch, IRX Therapeutics, New York/US
  • 6 Otolaryngology, Stanford University, Stanford/US
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Resources

Abstract 3874

Background

IRX-2 is an injectable cancer immunotherapy composed of cytokines purified from stimulated peripheral blood mononuclear cells. In a phase 2a trial (n = 27), neoadjuvant IRX-2 significantly increased lymphocyte infiltration (LI) into resected head and neck tumors. Increased LI was associated with changes in fibrosis and necrosis in resected tumors, 65% event-free survival (EFS) at 2 years, and 65% overall survival (OS) at 5 years, better than rates for historical matched controls. Patients with LI greater than the median had improved OS compared to those below the median. This substudy was undertaken to define the mechanisms responsible for the increase in LI with neoadjuvant IRX-2.

Methods

Matched pre- and post-treatment tumor specimens from 7 phase 2a study patients were interrogated with two immune-profiling technologies, multiplex immunohistochemistry (IHC, PerkinElmer, Waltham, MA) and transcriptome analysis (NanoString Technologies, Seattle, WA).

Results

Multiplex IHC provided detailed visualization and quantitation of various immune cells in the tumor microenvironment (TME), supporting previous phase 2a pathology findings. Transcriptome analysis provided a global snapshot of the TME, quantitative information on immune cell subsets, and insights into possible mechanisms for changes in LI. Consistent with IRX-2 activation of multiple immune cells in the TME, mRNA expression of B cell, CD4+ T cell, CD8+ T cell, and dendritic cell functional genes was increased on average by 87%, 106%, 6%, and 130%, respectively, following treatment with IRX-2. Increases in chemokine gene expression were observed, suggesting that IRX-2-induced production of chemokines may in part drive tumor LI. Strong evidence of functional immune activation uncovered by transcriptome analysis included an increase in interferon g pathway gene expression and induction of regulatory checkpoint pathways.

Conclusions

Neoadjuvant IRX-2 promotes tumor LI and prolongs EFS and OS in patients with head and neck squamous cell carcinoma. Immune profile analyses provided insights into the pathways potentially responsible for IRX-2-induced increases in LI and overall immune activation.

Clinical trial identification

Legal entity responsible for the study

IRX Therapeutics, Inc.

Funding

IRX Therapeutics, Inc

Disclosure

G.T. Wolf: Corporate sponsored research with IRX Therapeutics, Inc. J.G. Newman, M.J. Kaplan: Research funding IRX Therapeutics. N.L. Berinstein: Consultant, IRX Therapeutics. M.J. McNamara: Research funding IRX Therapeutics. J.E. Egan: Employed by IRX Therapeutics. All other authors have declared no conflicts of interest.

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