Locoregional response and increased natural killer activity after intratumoral injection of HLA-B7/beta2-microglobulin gene in patients with cancer.
The purpose of this study was to assess the therapeutic potential of injecting the gene for HLA-B7/beta2-microglobulin into the subcutaneous metastatic nodules of patients who are refractory to conventional treatments. The nine patients evaluated were divided into three groups and given escalating doses of DNA (20, 40, and 100 microg of the HLA-B7 plasmid DNA/lipid complex for each group) every 2 weeks. Biopsy specimens from the treated tumor nodules of all nine patients were positive for the presence of DNA and for HLA-B7 mRNA expression. Moreover, in six of the nine patients, immunohistology of tumor biopsy samples revealed the expression of recombinant HLA-B7 protein. Also, all nine patients showed an increase in NK activity in their circulating peripheral blood lymphocytes. In two lung cancer patients, one partial and one mixed response was observed after gene transfer. These responses were confined to the treated nodules and the untreated locoregional lymph nodes; the lung masses showed no regression. Remission durations were 14 and 6 weeks, respectively, and in a total of 35 cycles no significant toxicities were observed. Immunohistologic analysis revealed an increased infiltration of CD4+ T cells, macrophages, and NK cells after therapy. In two responding cases, direct intratumoral injection of an allogeneic class I gene could elicit an antitumor response in locoregional areas, possibly through the activation of NK cells.
Heo
D S
DS
Department Internal Medicine, Seoul National University Hospital, Cancer Research Center, Seoul National University Medical College, South Korea.
Yoon
S J
SJ
Kim
W S
WS
Lee
K H
KH
Seol
J G
JG
Lee
S G
SG
Jung
C W
CW
Cho
E K
EK
Kim
C W
CW
Park
M H
MH
Sung
M W
MW
Kim
K H
KH
Bang
Y J
YJ
Kim
N K
NK
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D018014:Gene Transfer Techniques; D005805:Genes, MHC Class I / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007267:Injections; D007694:Killer Cells, Natural / Q000276:immunology*; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D001613:beta 2-Microglobulin / Q000235:genetics*
D015703:Antigens, CD; D015235:HLA-B Antigens; D008081:Liposomes; D012333:RNA, Messenger; D001613:beta 2-Microglobulin