Alloantigen gene therapy for squamous cell carcinoma of the head and neck

Results of a phase 1 trial

Lyon L. Gleich, Jack L. Gluckman, Shanna Armstrong, Paul Williams Biddinger, Mary Ann Miller, Kamala Balakrishnan, Keith M. Wilson, Harold I. Saavedra, Peter J. Stambrook

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Objective: To determine the safety and efficacy of an immunogenic gene therapy using a drug designed to produce expression of a foreign class 1 major histocompatibility complex protein in patients with head and neck cancer. Design: Phase 1 prospective clinical trial Setting: Academic medical setting. Patients: Nine patients with advanced head and neck squamous cell carcinoma who had failed conventional therapy and did not express HLA-B7, a class I major histoeompatibility complex protein. Intervention: Patients were treated with Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection. Allovectin-7 contains a plasmid complementary DNA complexed with a cationic lipid, which results in expression of HLA-B7 Main Outcome Measures: Patients were assessed for any toxic effects and for any change in tumor volume. Biopsy specimens obtained before and after therapy were evaluated by immunohistochemistry to detect HLA-B7 expression and with the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate- biotin nick end labeling (TUNEL) assay to detect any induction of apoptosis. Results: There were no toxic effects of the gene therapy. In 4 of these 9 patients there was a partial response to treatment, evidenced by a gradual reduction in tumor size. One patient has remained alive for more than 17 months since commencing treatment, with no clinical evidence of disease but with persistent histological evidence of cancer. Analysis of the biopsy specimens from 2 of the patients who responded to therapy demonstrated HLA- B7 expression. The TUNEL assay demonstrated extensive apoptosis in both of these patients, suggesting that this may be the mechanism of tumor reduction. Conclusions: These data demonstrate the potential efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi-institutional study has been initiated to expand on these findings.

Original languageEnglish (US)
Pages (from-to)1097-1104
Number of pages8
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume124
Issue number10
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

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Isoantigens
Genetic Therapy
HLA-B7 Antigen
Poisons
In Situ Nick-End Labeling
Apoptosis
Biopsy
Therapeutics
Carcinoma, squamous cell of head and neck
Neoplasms
Clinical Trials, Phase I
Head and Neck Neoplasms
Biotin
Transferases
Tumor Burden
Major Histocompatibility Complex
Proteins
Plasmids
Complementary DNA
Immunohistochemistry

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

Alloantigen gene therapy for squamous cell carcinoma of the head and neck : Results of a phase 1 trial. / Gleich, Lyon L.; Gluckman, Jack L.; Armstrong, Shanna; Biddinger, Paul Williams; Miller, Mary Ann; Balakrishnan, Kamala; Wilson, Keith M.; Saavedra, Harold I.; Stambrook, Peter J.

In: Archives of Otolaryngology - Head and Neck Surgery, Vol. 124, No. 10, 01.01.1998, p. 1097-1104.

Research output: Contribution to journalArticle

Gleich, LL, Gluckman, JL, Armstrong, S, Biddinger, PW, Miller, MA, Balakrishnan, K, Wilson, KM, Saavedra, HI & Stambrook, PJ 1998, 'Alloantigen gene therapy for squamous cell carcinoma of the head and neck: Results of a phase 1 trial', Archives of Otolaryngology - Head and Neck Surgery, vol. 124, no. 10, pp. 1097-1104. https://doi.org/10.1001/archotol.124.10.1097
Gleich, Lyon L. ; Gluckman, Jack L. ; Armstrong, Shanna ; Biddinger, Paul Williams ; Miller, Mary Ann ; Balakrishnan, Kamala ; Wilson, Keith M. ; Saavedra, Harold I. ; Stambrook, Peter J. / Alloantigen gene therapy for squamous cell carcinoma of the head and neck : Results of a phase 1 trial. In: Archives of Otolaryngology - Head and Neck Surgery. 1998 ; Vol. 124, No. 10. pp. 1097-1104.
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AU - Biddinger, Paul Williams

AU - Miller, Mary Ann

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