Phase I Trial of sequential administration of recombinant DNA and adenovirus expressing L523S protein in early stage non-small-cell lung cancer.
L523S is an immunogenic lung cancer antigen that has demonstrated preclinical safety when the gene is injected intramuscularly as an expressive plasmid (pVAX/L523S) and when delivered following incorporation into an E1B-deleted adenovirus (Ad/L523S). We performed a phase I clinical trial in 13 stage IB, IIA, and IIB non-small-cell lung cancer patients. pVAX/L523S (8 mg on days 0 and 14 in all cohorts) and Ad/L523S (1, 20, 400 x 10(9) vp on days 28 and 56, cohorts 1, 2, and 3, respectively) were administered to 3 patients in each of three cohorts. No significant toxic effect was identified. All but 1 patient demonstrated greater than or equal to twofold elevation in anti-adenovirus antibodies. One of 10 evaluable patients demonstrated L523S-specific antibody by direct IgG ELISA. Two patients developed disease recurrence and all remain alive after a median of 290 days follow-up. Results suggest a high level of safety but evidence of L523S-directed immune activation was limited, suggesting a need for modification of dose, schedule, and site of vaccination (i.e., intradermal) with further clinical testing.
Mary Crowley Medical Research Center, Texas Oncology PA, Dallas, TX 75201, USA. jnemunaitis@mcmrc.com
John
J
Nemunaitis
Thomas
T
Meyers
Neil
N
Senzer
Casey
C
Cunningham
Howard
H
West
Eric
E
Vallieres
Stephen
S
Anthony
Svetislava
S
Vukelja
Barry
B
Berman
Heather
H
Tully
Beena
B
Pappen
Stephen
S
Sarmiento
Rosemarie
R
Arzaga
Steven
S
Duniho
Susan
S
Engardt
Madeleine
M
Meagher
Martin A
MA
Cheever
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000628:therapy*; D004274:DNA, Recombinant / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology
D004274:DNA, Recombinant; C473444:L523S protein, human; D016601:RNA-Binding Proteins