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A phase I clinical trial of immunotherapy with interferon-γ gene-modified autologous melanoma cells : Monitoring the humoral immune response

✍ Scribed by Zeinab Abdel-Wahab; Christina Weltz; Dina Hester; Nancy Pickett; Carol Vervaert; Jack R. Barber; Douglas Jolly; Hilliard F. Seigler


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
208 KB
Volume
80
Category
Article
ISSN
0008-543X

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✦ Synopsis


and then 18 million for the fifth and sixth injections. The humoral immune responses of the patients were assessed by enzyme-linked immunoadsorbent assay, radioimmunoassay, and radioimmunoprecipitation.

RESULTS.

Thirteen of the 20 patients completed the immunization protocol. Eight of these 13 patients showed a humoral immunoglobulin (Ig)G response against autologous and allogeneic melanoma cells. The other five patients either had no detectable antimelanoma antibodies or showed a weak IgG response that did not rise significantly above the preimmune level. All the sera contained low or undetectable levels of antimelanoma IgM antibodies. The IgG response increased progressively in titer during the course of immunization. The positive sera showed preferentially strong binding to melanoma cell lines and some cross-reactivity to nonmelanoma tumors. A 75-80 kD antigen on melanoma cells was immunoprecipitated by postimmune sera of 3 of the responding patients. Preimmune sera from Presented in abstract form at a meeting of the these three patients and sera from other patients immunized with a standard American Association for Cancer Research, nontransduced melanoma cell vaccine failed to precipitate this antigen. Two pa-Washington, DC, April 1996. tients with significant increases in serum IgG had clinical tumor regression, and two additional patients with low serum IgG response had transient shrinkage of Supported in part by National Cancer Institute nodular disease during therapy. grant no. 1RO1-CA-64959-01 and by Depart-CONCLUSIONS. These data suggest that gene therapy with IFN-g-transduced melament of Veterans Affairs grant no. Seigler 0001. noma cells is safe and worthy of further investigation in patients with less advanced Address for reprints: Zeinab Abdel-Wahab, stage malignant melanoma. The ability to monitor changes in the humoral responses M.B., Ch.B., Ph.D., Department of Surgery, Box of the immunized patients has been demonstrated. Cancer 1997;80:401-12.