Cellular and humoral immune responses to adenovirus and p53 protein antigens in patients following intratumoral injection of an adenovirus vector expressing wild-type. P53 (Ad-p53).
The immune responses of 10 patients with advanced non-small cell lung cancer receiving monthly intratumoral injections of a recombinant adenovirus containing human wild-type p53 (Ad-p53) to adenovirus and transgene antigens were studied. The predominate cellular and humoral immune responses as measured by lymphocyte proliferation and neutralizing antibody (Ab) formation were to adenovirus serotype 5 vector antigens, with increased responses in posttreatment samples. Consistent alterations in posttreatment cellular and humoral immune responses to p53 epitopes were not observed, and cytotoxic Abs to human lung cancer cells were not generated. Patients in this study had evidence of an antitumoral effect of this treatment with prolonged tumor stability or regression; however, neither Abs to p53 protein nor increased lymphocyte proliferative responses to wild-type or mutant p53 peptides have been consistently detected.
Yen
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Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Ioannides
C G
CG
Xu
K
K
Swisher
S G
SG
Lawrence
D D
DD
Kemp
B L
BL
El-Naggar
A K
AK
Cristiano
R J
RJ
Fang
B
B
Glisson
B S
BS
Hong
W K
WK
Khuri
F R
FR
Kurie
J M
JM
Lee
J J
JJ
Lee
J S
JS
Merritt
J A
JA
Mukhopadhyay
T
T
Nesbitt
J C
JC
Nguyen
D
D
Perez-Soler
R
R
Pisters
K M
KM
Putnam
J B
JB
Schrump
D S
DS
Shin
D M
DM
Walsh
G L
GL
Roth
J A
JA
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000368:Aged; D000595:Amino Acid Sequence; D000917:Antibody Formation; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53