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[Cancer Research 61, 6451-6458, September 1, 2001]
© 2001 American Association for Cancer Research

Immunology

Immune and Clinical Responses in Patients with Metastatic Melanoma to CD34+ Progenitor-derived Dendritic Cell Vaccine1

Jacques Banchereau2,3, A. Karolina Palucka2, Madhav Dhodapkar2, Susan Burkeholder, Nicolas Taquet, Alexandre Rolland, Sybil Taquet, Sebastien Coquery, Knut M. Wittkowski, Nina Bhardwaj, Luis Pineiro, Ralph Steinman and Joseph Fay

Baylor Institute for Immunology Research, Dallas, Texas 75204 [J. B., A. K. P., S. B., N. T., A. R., S. T., S. C., L. P., J. F.]; Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399 [M. D., N. B., R. S.]; and General Clinical Research Center, The Rockefeller University Hospital, New York, New York 10021-6399 [K. M. W.]

Immunization to multiple defined tumor antigens for specific immune therapy of human cancer has thus far proven difficult. Eighteen HLA A*0201+ patients with metastatic melanoma received injections s.c. of CD34+progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells. DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological effects were assessed by comparing response profiles using marginal likelihood scores. DC injections were well tolerated except for progressive vitiligo in two patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16 of 18 patients. An enhanced immune response to one or more MelAgs was seen in these same 16 patients, including 10 patients who responded to >2 MelAgs. The two patients failing to respond to both control and tumor antigens experienced rapid tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with immunity to two or less MelAgs had progressive disease 10 weeks after study entry, in contrast to tumor progression in only 1 of 10 patients with immunity to >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these patients. The overall immunity to MelAgs after DC vaccination is associated with clinical outcome (P = 0.015).




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J. Taieb, K. Maruyama, C. Borg, M. Terme, L. Zitvogel, S. Appel, and P. Brossart
Imatinib mesylate impairs Flt3L-mediated dendritic cell expansion and antitumor effects in vivo
Blood, March 1, 2004; 103(5): 1966 - 1967.