PMID- 10807351
OWN - NLM
STAT- MEDLINE
DCOM- 20000518
LR  - 20121115
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 110
IP  - 5 Pt 1
DP  - 2000 May
TI  - Gene therapy for head and neck cancer.
PG  - 708-26
AB  - OBJECTIVES/HYPOTHESIS: New treatment methods are needed for head and neck cancer 
      to improve survival without increasing morbidity. Gene therapy is a potential 
      method of improving patient outcome. Progress in gene therapy for cancer is 
      reviewed with emphasis on the limitations of vector technology and treatment 
      strategies. Given the current technological vector limitations in transmitting 
      the therapeutic genes, treatments that require the fewest number of cells to be 
      altered by the new gene are optimal. Therefore an immune-based gene therapy 
      strategy was selected in which the tumors were transfected with the gene for an 
      alloantigen, human leukocyte antigen (HLA)-B7, a class I major histocompatibility 
      complex (MHC). This would restore an antigen presentation mechanism in the tumor 
      to induce an antitumor response. This gene therapy strategy was tested in 
      patients with advanced, unresectable head and neck cancer. STUDY DESIGN: 
      Prospective trial. METHODS: Twenty patients with advanced head and neck cancer 
      who had failed conventional therapy and did not express HLA-B7 were treated with 
      gene therapy using a lipid vector by direct intratumoral injection. The gene 
      therapy product contained the HLA-B7 gene and the beta2-microglobulin gene, which 
      permits complete expression of the class I MHC at the cell surface. Patients were 
      assessed for any adverse effects, for changes in tumor size, for time to disease 
      progression, and for survival. Biopsy specimens were assessed for pathological 
      response, HLA-B7 expression, apoptosis, cellular proliferation, CD-8 cells, 
      granzyme, and p53 status. RESULTS: There were no adverse effects from the gene 
      therapy. At 16 weeks after beginning gene therapy, four patients had a partial 
      response and two patients had stable disease. Two of the tumors completely 
      responded clinically, but tumor was still seen on pathological examination. The 
      time to disease progression in the responding patients was 20 to 80 weeks. The 
      median survival in patients who completed gene therapy was 54 weeks, compared 
      with 21 weeks in patients whose tumors progressed after the first cycle of 
      treatment. One patient survived for 106 weeks without any additional therapy. 
      HLA-B7 was demonstrated in the treated tumors, and increased apoptosis was seen 
      in the responding tumors. CONCLUSION: Significant advances have been made in the 
      field of gene therapy for cancer. Alloantigen gene therapy has had efficacy in 
      the treatment of cancer and can induce tumor responses in head and neck tumors. 
      Alloantigen gene therapy has significant potential as an adjunctive treatment of 
      head and neck cancer.
FAU - Gleich, L L
AU  - Gleich LL
AD  - Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati 
      Medical Center, Ohio 45267-0528, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Allovectin-7)
RN  - 0 (DNA, Recombinant)
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (Lipids)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Apoptosis/genetics
MH  - Carcinoma, Squamous Cell/genetics/mortality/pathology/*therapy
MH  - *DNA
MH  - DNA, Recombinant
MH  - Female
MH  - Follow-Up Studies
MH  - *Genetic Therapy/methods
MH  - HLA-B7 Antigen/genetics
MH  - Humans
MH  - Lipids/*therapeutic use
MH  - Lymph Nodes/pathology
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Otorhinolaryngologic Neoplasms/genetics/mortality/pathology/*therapy
MH  - Plasmids/*therapeutic use
MH  - Survival Rate
MH  - Treatment Outcome
RF  - 176
EDAT- 2000/05/12 09:00
MHDA- 2000/05/20 09:00
CRDT- 2000/05/12 09:00
PHST- 2000/05/12 09:00 [pubmed]
PHST- 2000/05/20 09:00 [medline]
PHST- 2000/05/12 09:00 [entrez]
AID - 10.1097/00005537-200005000-00002 [doi]
PST - ppublish
SO  - Laryngoscope. 2000 May;110(5 Pt 1):708-26. doi: 10.1097/00005537-200005000-00002.