A phase I clinical trial of immunotherapy with interferon-? gene-modified autologous melanoma cells

Abstract

consisted of 2 million cells, followed by 6 million for the third and fourth injections, 2 Chiron Viagene Inc., San Diego, California.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 paWashington, 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.

Heparin Induces Differentiation of CD1a+ Dendritic Cells from Monocytes: Phenotypic and Functional Characterization

“…8), the results reported in this work indicate that heparin-treated DCs have higher priming activity for T cells to produce both type 1 and type 2 cytokines (Table I). Although immune polarization to Th1 response has been associated with the development of cytotoxic T cells and protective antitumor immunity (38), the induction of Th2 response could confer humoral immunity for Ab-mediated cytotoxicity (39), which may provide additional immune protection against tumor growth. Because heparin-treated DCs could prime T cells for type 1 and type 2 cytokine responses (Table I) and are more potent than heparin-untreated DCs to stimulate proliferation of T cells (Fig.…”

Targeting tumor vasculature endothelial cells and tumor cells for immunotherapy of human melanoma in a mouse xenograft model

“…The scFv molecules were isolated from a fusion-phage display library derived from the antibody repertoire of a melanoma patient who was vaccinated with autologous tumor cells (2,3). The cognate antigen for the immunoconjugates is the melanoma-associated chondroitin sulfate proteoglycan MCSP, which is expressed predominately on the surface of most melanoma cells (1,4).…”

Immunomodulation of cancer: potential use of selectively replicating agents

“…A similar picture is emerging from phase I studies of vaccination of patients with cancer with transduced human tumor cells. Even though the approach itself is safe, the available results show that only about 10% of patients displayed an objective response (14)(15)(16).…”