Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer.
OBJECTIVE
The initial goal of this study was to test the immunologic and clinical effects of a new cancer vaccine consisting of dendritic cells (DC) transduced with the full-length wild-type p53 gene delivered via an adenoviral vector in patients with extensive stage small cell lung cancer.


METHODS
Twenty-nine patients with extensive stage small cell lung cancer were vaccinated repeatedly at 2-week intervals. Most of the patients received three immunizations. p53-specific responses were evaluated, and phenotype and function of T cells, DCs, and immature myeloid cells were analyzed and correlated with antigen-specific immune responses. Objective clinical response to vaccination as well as subsequent chemotherapy was evaluated.


RESULTS
p53-specific T cell responses to vaccination were observed in 57.1% of patients. Immunologic responses to vaccination were positively associated with a moderate increase in the titer of antiadenovirus antibodies, and negatively with an accumulation of immature myeloid cells. One patient showed a clinical response to vaccination whereas most of the patients had disease progression. However, we observed a high rate of objective clinical responses to chemotherapy (61.9%) that immediately followed vaccination. Clinical response to subsequent chemotherapy was closely associated with induction of immunologic response to vaccination.


CONCLUSIONS
This study provides clinical support for an emerging paradigm in cancer immunotherapy, wherein optimal use of vaccination might be more effective, not as a separate modality, but in direct combination with chemotherapy.
Antonia
Scott J
SJ
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Mirza
Noweeda
N
Fricke
Ingo
I
Chiappori
Alberto
A
Thompson
Patricia
P
Williams
Nicholas
N
Bepler
Gerold
G
Simon
George
G
Janssen
William
W
Lee
Ji-Hyun
JH
Menander
Kerstin
K
Chada
Sunil
S
Gabrilovich
Dmitry I
DI
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000276:immunology; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
D019496:Cancer Vaccines; D016159:Tumor Suppressor Protein p53