Z. Abdelwahab et al., A PHASE-I CLINICAL-TRIAL OF IMMUNOTHERAPY WITH INTERFERON-GAMMA GENE-MODIFIED AUTOLOGOUS MELANOMA-CELLS - MONITORING THE HUMORAL IMMUNE-RESPONSE, Cancer, 80(3), 1997, pp. 401-412
BACKGROUND. Tumor cells transduced with cytokine genes provide immunog
enic vaccines for cancer immunotherapy. METHODS. A Phase I clinical tr
ial was conducted for the specific active immunization of melanoma pat
ients with interferon-gamma (IFN-gamma) gene-modified autologous melan
oma tumor cells. Short term melanoma cultures were transduced retrovir
ally with the gene for human IFN-gamma. The genetically modified melan
oma cells secreted biologically active IFN-gamma and showed enhanced e
xpression of major histocompatibility complex class I and class II sur
face antigens. These cells were inactivated by irradiation (50 gray) a
nd were cryopreserved for the vaccine. Twenty melanoma patients were e
nrolled in this clinical trial. The immunizations were administered in
escalating doses once every 2 weeks for 3 months. The first and secon
d injections consisted of 2 million cells, followed by 6 million for t
he third and fourth injections, and then 18 million for the fifth and
sixth injections. The humoral immune responses of the patients were as
sessed by enzyme-linked immunoadsorbent assay, radioimmunoassay, and r
adioimmunoprecipitation. RESULTS. Thirteen of the 20 patients complete
d the immunization protocol. Eight of these 13 patients showed a humor
al immunoglobulin (Ig)G response against autologous and allogeneic mel
anoma cells. The other five patients either had no detectable antimela
noma antibodies or showed a weak IgG response that did not rise signif
icantly above the preimmune level. All the sera contained low or undet
ectable levels of antimelanoma IgM antibodies. The IgG response increa
sed progressively in titer during the course of immunization. The posi
tive sera showed preferentially strong binding to melanoma cell lines
and some cross-reactivity to nonmelanoma tumors. A 75 -80 kD antigen o
n melanoma cells was immunoprecipitated by postimmune sera of 3 of the
responding patients. Preimmune sera from these three patients and ser
a from other patients immunized with a standard nontransduced melanoma
cell vaccine failed to precipitate this antigen. Two patients with si
gnificant increases in serum IgG had clinical tumor regression, and tw
o additional patients with low serum IgG response had transient shrink
age of nodular disease during therapy. CONCLUSIONS. These data suggest
that gene therapy with IFN-gamma-transduced melanoma cells is safe an
d worthy of further investigation in patients with less advanced stage
malignant melanoma The ability to monitor changes in the humoral resp
onses of the immunized patients has been demonstrated. (C) 1997 Americ
an Cancer Society.