Correlation of immune responses and survival in a phase II study of belagenpumatucel-L in non-small cell lung cancer.

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Author(s): H. Fakhrai,
A. Tong, J. Nemunaitis, D. L. Shawler; NovaRx, San Diego, CA; Baylor
Health Science Center, Dallas, TX; Mary Crowley Medical Research
Center, Dallas, TX
Belagenpumatucel-L (Lucanix), a therapeutic vaccine comprised of 4
TGF-?2 antisense gene-modified allogeneic non-small cell lung cancer
(NSCLC) cell lines, was tested in a phase II trial in which subjects
with stage IIIB/IV NSCLC received intradermal injections of the vaccine
every 4-8 weeks.
Methods: We performed 2 cellular immunity
assays and 2 humoral immunity assays on subjects in the trial. To
measure the overall immune status, pretreatment peripheral blood
mononuclear cells (PBMC) were stimulated by PMA/ionomycin and assessed
by formation of IFN-? ELISPOT. We also measured in vitro IFN-? ELISPOT
formation by subjects' PBMC following vaccination. The two humoral
assays looked at the induction of anti-belagenpumatucel-L antibodies
and anti-HLA antibodies.
Results: Subjects were classified as immune response positive (IR+)
if they were positive for 3 or 4 of the assays described above. The
remaining subjects were classified as immune response negative (IR-). There were 11 subjects who were IR+ and 24 who were IR-negative. The IR+ subjects had a median survival of 32.5 months (95% CI, 25.2 to 39.8) compared to 11.6 months (95% CI, 5.6 to 17.6) for IR-
subjects (p=0.011, log-rank test). Subjects were also classified as
clinical responders or nonresponders based on their tumor assessment
after 4 months on trial. 10/19 subjects classified as clinical
responders were IR+ compared to only 1/16 nonresponders (p=0.004, Fisher's exact test).
These data demonstrate a strong correlation between the achievement of
a combination of cellular and humoral immune responses and a
significant increase in overall survival in the subjects treated with
belagenpumatucel-L and suggest that both components of the immune
system are important for the induction of clinically significant
antitumor immunity by the vaccine.