N. Habal et al., CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer, ANN SURG O, 8(5), 2001, pp. 389-401
Background: The immunogenicity of the polyvalent tumor cell vaccine CancerV
ax has been correlated with the survival of patients receiving active immun
otherapy for melanoma. Because the various antigens expressed on the vaccin
e are common to colon adenocarcinoma cells, we examined the survival impact
of immune responses elicited by CancerVax in patients with advanced colon
cancer refractory to standard therapy.
Methods: Twenty-seven patients with American Joint Committee on Cancer (AJC
C) stage IV colorectal adenocarcinoma were entered prospectively into the s
tudy. CancerVax was coadministered with bacille Calmette-Guerin (BCG) for t
he first 2 weeks of vaccine treatment. Blood was drawn at the start of ther
apy and every 2 weeks thereafter to measure serum titers of immunoglobulin
(Ig)G and IgM against TA90 (a 90-kD immunogen common to colon cancer and Ca
ncerVax cells) and against purified protein derivative (PPD), a nontumor co
ntrol antigen. Cellular immune responses were evaluated by delayed-type hyp
ersensitivity (DTH) reaction to vaccine cells and to PPD. Mean follow-up ti
me was 17.5 months.
Results: There was a significant (P = .0001) increase in anti-TA90 IgG and
IgM titers and in DTH response to vaccine cells. Humoral and skin responses
to TA90 did not correlate with responses to PPD (P = .199 for IgM, P = .95
8 for IgG, and P = .149 for DTH). This suggests that these responses are no
t a manifestation of general immune competence. The median overall survival
(OS) was 21.9 months for the entire group. Overall survival was higher amo
ng patients whose IgM(TA90) titer was > 800 (P = .003) or whose disease-fre
e interval exceeded 12 months (P = .031). Multivariate Cox regression analy
sis-using age, sex, disease-free interval, disease status, extent of metast
asis, humoral responses, and DTH responses-found only peak IgM(TA90) titer
to be a significant predictor of overall survival (P = .0365).
Conclusions: CancerVax can induce measurable humoral and cellular immune re
sponses to tumor-associated antigens in patients with advanced-stage colon
cancer. These responses correlate with overall survival. This novel therape
utic regimen for patients with advanced colon cancer merits further investi
gation.