A PHASE-I CLINICAL-TRIAL OF IMMUNOTHERAPY WITH INTERFERON-GAMMA GENE-MODIFIED AUTOLOGOUS MELANOMA-CELLS - MONITORING THE HUMORAL IMMUNE-RESPONSE

Citation
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
Citations number
40
Categorie Soggetti
Oncology
Journal title
CancerACNP
ISSN journal
0008543X
Volume
80
Issue
3
Year of publication
1997
Pages
401 - 412
Database
ISI
SICI code
0008-543X(1997)80:3<401:APCOIW>2.0.ZU;2-E
Abstract
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.