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A phase 1/2a study to test the safety and immunogenicity of a p16 INK4a peptide vaccine in patients with advanced human papillomavirus‐associated cancers
Author(s) -
Reuschenbach Miriam,
Pauligk Claudia,
Karbach Julia,
Rafiyan MohammadReza,
Kloor Matthias,
Prigge ElenaSophie,
Sauer Madeleine,
AlBatran SalahEddin,
Kaufmann Andreas M.,
Schneider Achim,
Jäger Elke,
von Knebel Doeberitz Magnus
Publication year - 2016
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.29925
Subject(s) - medicine , immunogenicity , adverse effect , vaccination , cancer , immunology , antibody , peptide vaccine , oncology , antigen , immune system , epitope
BACKGROUND The cyclin‐dependent kinase inhibitor p16 INK4a is strongly and consistently overexpressed in all human papillomavirus (HPV)‐associated cancers. Therefore, the authors hypothesized that p16 INK4a may be a vaccine target antigen for HPV‐associated cancers. To test this hypothesis, the authors performed a phase 1/2a first‐in‐human trial to evaluate the safety and immunogenicity of a p16 INK4a ‐based peptide vaccine. METHODS A total of 26 patients with different, advanced, p16 INK4a ‐overexpressing, HPV DNA‐positive cancers were included after the completion of standard treatment. According to protocol, 12 subcutaneous injections of a p16 INK4 peptide (P16_37‐63) mixed in a water‐in‐oil emulsion with immunoadjuvant activity (Montanide ISA‐51 VG) were administered over a 6‐month period. RESULTS A total of 20 patients received at least 4 injections and were evaluable for immune responses against P16_37‐63. Clusters of differentiation (CD) 4 T cells were detected in 14 of 20 patients (3 of whom had preexisting CD4 T cells before vaccination), CD8 T cells were detected in 5 of 20 patients, and antibodies were detected in 14 of 20 patients (1 of whom had preexisting antibodies). No suspected unexpected serious adverse reaction or serious adverse drug reaction was documented. All reported serious adverse events were expected and not considered to be related to study therapy. None of the patients discontinued trial participation due to unacceptable toxicities and no dose‐limiting toxicities occurred. Tumor response could be assessed in 14 patients. Of these, 9 patients (64%) had stable disease as their best overall response and 5 patients (36%) developed progressive disease. CONCLUSIONS Vaccination with the p16 INK4a ‐derived peptide P16_37‐63 appears to induce cellular and humoral immune responses and does not cause severe toxicities. The results of the current study pave the way for the further clinical development of p16 INK4a ‐based cancer immunotherapeutics. Cancer 2016;122:1425–1433 . © 2016 American Cancer Society .