A Phase I Trial of Tumor Lysate-pulsed Dendritic Cells in the Treatment of Advanced Cancer

• Published in: Clinical cancer research 2002-04, Vol.8 (4), p.1021-1032
• Main Authors: CHANG, Alfred E, REDMAN, Bruce G, WHITFIELD, Joel R, NICKOLOFF, Brian J, BRAUN, Thomas M, LEE, Peter P, GEIGER, James D, MULE, James J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, CD - analysis; Antineoplastic agents; B7-2 Antigen; Biological and medical sciences; CD40 Antigens - analysis; CD83 Antigen; Dendritic Cells - immunology; Female; Flow Cytometry; Hemocyanins - immunology; HLA-DR Antigens - analysis; Humans; Hypersensitivity, Delayed - immunology; Immunoglobulins - analysis; Immunophenotyping; Immunotherapy; Immunotherapy, Adoptive; Leukocytes, Mononuclear - immunology; Lipopolysaccharide Receptors - analysis; Major Histocompatibility Complex - immunology; Male; Medical sciences; Membrane Glycoproteins - analysis; Middle Aged; Neoplasm Staging; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - therapy; Peptide Fragments - immunology; Pharmacology. Drug treatments; Treatment Outcome; Vaccination
• ISSN: 1078-0432; 1557-3265

Purpose: The objectives of this study were to assess the toxicity and immunologicalresponse induced by the intradermal (i.d) administration of tumor lysate-pulsed dendritic cells (DCs). Experimental Design: Patients with stage IV solid malignancies were treated in cohorts that received 10 6 , 10 7 , and 10 8 DCs i.d. every 2 weeks for three vaccines. Each vaccine was composed of a mixture of half DCs pulsed with autologous tumor lysate and the other half with keyhole limpet hemocyanin (KLH). Peripheral blood mononuclear cells (PBMCs) harvested 1 month after the last immunization was compared with pretreatment PBMCs for immunological response. Delayed-type hypersensitivity reactivity to tumor antigen and KLH was also assessed. Results: Fourteen patients received all three vaccines and were evaluable for toxicity and/or immunological monitoring. There were no grade 3 or 4 toxicities associated with the vaccines or major evidence of autoimmunity. Local accumulation of CD4 + and CD8 + T cells were found at the vaccination sites. There was a significant proliferative response of PBMCs to KLH induced by the vaccine. In 5 of 6 patients, the vaccine resulted in increased IFN-γ production by PBMCs to KLH in an ELISPOT assay. Using the same assay, 3 of 7 patients’ PBMCs displayed increased IFN-γ production in response to autologous tumor lysate. One patient with melanoma also was observed to have an increased frequency of MART-1- and gp100-reactive CD8 + T cells after vaccination. By delayed-type hypersensitivity testing, 8 of 9 and 4 of 10 patients demonstrated reactivity to KLH and autologous tumor, respectively. Two patients with melanoma experienced a partial and a minor response, respectively. Conclusion: The administration of tumor lysate-pulsed DCs is nontoxic and capable of inducing immunological response to tumor antigen. Additional studies are necessary to improve tumor rejection responses.