CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer.
BACKGROUND
The immunogenicity of the polyvalent tumor cell vaccine CancerVax has been correlated with the survival of patients receiving active immunotherapy for melanoma. Because the various antigens expressed on the vaccine 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 (AJCC) stage IV colorectal adenocarcinoma were entered prospectively into the study. CancerVax was coadministered with bacille Calmette-Guerin (BCG) for the first 2 weeks of vaccine treatment. Blood was drawn at the start of therapy 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 CancerVax cells) and against purified protein derivative (PPD), a nontumor control antigen. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) reaction to vaccine cells and to PPD. Mean follow-up time 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 = .958 for IgG, and P = .149 for DTH). This suggests that these responses are not a manifestation of general immune competence. The median overall survival (OS) was 21.9 months for the entire group. Overall survival was higher among patients whose IgMTA90 titer was >800 (P = .003) or whose disease-free interval exceeded 12 months (P = .031). Multivariate Cox regression analysis-using age, sex, disease-free interval, disease status, extent of metastasis, humoral responses, and DTH responses-found only peak IgMTA90 titer to be a significant predictor of overall survival (P = .0365).


CONCLUSIONS
CancerVax can induce measurable humoral and cellular immune responses to tumor-associated antigens in patients with advanced-stage colon cancer. These responses correlate with overall survival. This novel therapeutic regimen for patients with advanced colon cancer merits further investigation.
Habal
N
N
Sonya Valley Ghidossi Vaccine Laboratory of the Roy E. Coats Research Laboratories, Santa Monica, California 90404, USA.
Gupta
R K
RK
Bilchik
A J
AJ
Yee
R
R
Leopoldo
Z
Z
Ye
W
W
Elashoff
R M
RM
Morton
D L
DL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013997:Time Factors; D017778:Vaccines, Combined
D000951:Antigens, Neoplasm; D001500:BCG Vaccine; D019496:Cancer Vaccines; C113885:TA90 immune complex; D017778:Vaccines, Combined; C094534:polyvalent melanoma cell vaccine