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IRX-2 natural cytokine biologic for immunotherapy in patients with head and neck cancers

Authors Wolf GT, Moyer JS, Kaplan MJ, Newman JG, Egan JE, Berinstein NL, Whiteside TL

Received 13 February 2018

Accepted for publication 8 April 2018

Published 28 June 2018 Volume 2018:11 Pages 3731—3746


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Samir Farghaly

Gregory T Wolf,1 Jeffrey S Moyer,1 Michael J Kaplan,2 Jason G Newman,3 James E Egan,4 Neil L Berinstein,4 Theresa L Whiteside5

1Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, 2Department of Otolaryngology-Head and Neck Surgery, Stanford University Medical Center, Stanford, CA, 3Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, 4IRX Therapeutics, New York, NY, 5Department of Immunology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

Abstract: Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy characterized by tumor-driven immune-system abnormalities that contribute to disease progression. For patients with surgically resectable HNSCC, treatment is often curative surgery followed by irradiation or chemoradiation in high-risk settings to reduce the risk of recurrence. Poor survival and considerable morbidity of current treatments suggest the need for new therapeutic modalities that can improve outcomes. Defects in antitumor immunity of HNSCC patients include suppressed dendritic cell (DC) maturation, deficient antigen-presenting cell function, compromised natural killer (NK)-cell cytotoxicity, increased apoptosis of activated T lymphocytes, and impaired immune-cell migration to tumor sites. Strategies for relieving immunosuppression and restoring antitumor immune functions could benefit HNSCC patients. IRX-2 is a primary cell-derived biologic consisting of physiologic levels of T-helper type 1 cytokines produced by stimulating peripheral blood mononuclear cells of normal donors with phytohemagglutinin. The primary active components in IRX-2 are IL2, IL1β, IFNγ, and TNFα. In vitro, IRX-2 acts on multiple immune-system cell types, including DCs, T cells, and NK cells, to overcome tumor-mediated immunosuppression. In clinical settings, IRX-2 is administered as part of a 21-day neoadjuvant regimen, which includes additional pharmacologic agents (low-dose cyclophosphamide, indomethacin, and zinc) to promote anticancer immunoresponses. In a Phase IIA trial in 27 patients with surgically resectable, previously untreated HNSCC, neoadjuvant IRX-2 increased infiltration of T cells, B cells, and DCs into tumors and was associated with radiological reductions in tumor size. Event-free survival was 64% at 2 years, and overall 5-year survival was 65%. Follow-up and data analysis are under way in the multicenter, randomized, Phase IIB INSPIRE trial evaluating the IRX-2 regimen as a stand-alone therapy for activating the immune system to recognize and attack tumors.

Keywords: head and neck cancer, head and neck squamous cell carcinoma, immunotherapy, cytokines, lymphocytic infiltration, dendritic cells, T cells

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