Immunotherapy targeting HPV16/18 generates potent immune responses in HPV-associated head and neck cancer

Charu Aggarwal, Roger B. Cohen, Matthew P. Morrow, Kimberly A. Kraynyak, Albert J. Sylvester, Dawson M. Knoblock, Joshua M. Bauml, Gregory S. Weinstein, Alexander Lin, Jean Boyer, Lindsay Sakata, Sophie Tan, Aubrey Anton, Kelsie Dickerson, Drishty Mangrolia, Russell Vang, Michael Dallas, Sandra Oyola, Susan Duff, Mark EsserRakesh Kumar, David Weiner, Ildiko Csiki, Mark L. Bagarazzi

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Clinical responses with programmed death (PD-1) receptor–directed antibodies occur in about 20% of patients with advanced head and neck squamous cell cancer (HNSCCa). Viral neoantigens, such as the E6/E7 proteins of HPV16/18, are attractive targets for therapeutic immunization and offer an immune activation strategy that may be complementary to PD-1 inhibition. Patients and Methods: We report phase Ib/II safety, tolerability, and immunogenicity results of immunotherapy with MEDI0457 (DNA immunotherapy targeting HPV16/18 E6/E7 with IL12 encoding plasmids) delivered by electroporation with CELLECTRA constant current device. Twenty-two patients with locally advanced, p16þ HNSCCa received MEDI0457. Results: MEDI0457 was associated with mild injection site reactions, but no treatment-related grade 3–5 adverse events (AE) were noted. Eighteen of 21 evaluable patients showed elevated antigen-specific T-cell activity by IFNg ELISpot, and persistent cellular responses surpassing 100 spot-forming units (SFUs)/106 peripheral blood mononuclear cells (PBMCs) were noted out to 1 year. Induction of HPV-specific CD8þ T cells was observed. MEDI0457 shifted the CD8þ/FoxP3þ ratio in 4 of 5 post immunotherapy tumor samples and increased the number of perforinþ immune infiltrates in all 5 patients. One patient developed metastatic disease and was treated with anti–PD-1 therapy with a rapid and durable complete response. Flow-cytometric analyses revealed induction of HPV16-specific PD-1þ CD8þ T cells that were not found prior to MEDI0547 (0% vs. 1.8%). Conclusions: These data demonstrate that MEDI0457 can generate durable HPV16/18 antigen-specific peripheral and tumor immune responses. This approach may be used as a complementary strategy to PD-1/PD-L1 inhibition in HPV-associated HNSCCa to improve therapeutic outcomes.

Original languageEnglish (US)
Pages (from-to)110-124
Number of pages15
JournalClinical Cancer Research
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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