Optimizing dendritic cell-based immunotherapy in multiple myeloma: intranodal injections of idiotype-pulsed CD40 ligand-matured vaccines led to induction of type-1 and cytotoxic T-cell immune responses in patients

Autor: Nancy Rosen, Michele Cottler-Fox, Guido Tricot, Bart Barlogie, Sanjaya Viswamitra, Frits van Rhee, Qing Yi, Susann Szmania, Jianfei Qian, John Freeman
Rok vydání: 2010
Předmět:
Zdroj: British Journal of Haematology. 150:554-564
ISSN: 0007-1048
DOI: 10.1111/j.1365-2141.2010.08286.x
Popis: Vaccination with idiotype (Id) protein-pulsed dendritic cells (DCs) has been explored in multiple myeloma and the results have been disappointing. To improve the efficacy of DC vaccination in myeloma, we investigated the use of Id- and keyhole limpet haemocyanin (KLH)-pulsed, CD40 ligand-matured DCs administered intranodally. Nine patients with smoldering or stable myeloma without treatment were enrolled and DC vaccines were administered at weekly intervals for a total of 4 doses. Following vaccination, all patients mounted Id-specific γinterferon T-cell response. Interleukin-4 response was elicited in 2, and skin delayed-type hypersensitivity reaction occurred in 7 patients. More importantly, Id-specific cytotoxic T-cell responses were also detected in 5 patients. Most if not all patients mounted a positive T-cell response to KLH following vaccination. At one-year follow-up, 6 of the 9 patients had stable disease, while 3 patients had slowly progressive disease even during the vaccination period. At 5-year follow-up, 4 of the 6 patients continued with stable disease. No major side effects were noted. In summary, intranodal administration of Id-pulsed CD40 ligand-matured DCs was able to induce Id-specific T and B-cell responses in patients. Current efforts are geared towards breaking tumour-mediated immune suppression and improving clinical efficacy of this immunotherapy.
Databáze: OpenAIRE