Article

Autologous large multivalent immunogen vaccine in patients with metastatic melanoma and renal cell carcinoma.

Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware St. SE, MMC 480, Minneapolis, MN 55455, USA.
American journal of clinical oncology (Impact Factor: 2.21). 05/2008; 31(2):173-81. DOI: 10.1097/COC.0b013e3181573e6b
Source: PubMed

ABSTRACT To evaluate the safety and activity of large multivalent immunogen (LMI), prepared by immobilizing autologous tumor cell plasma membrane on 5-microm diameter silica beads, in patients with melanoma and renal cell carcinoma (RCC).
Thirty patients with stage IV metastatic melanoma and 31 patients with stage IV RCC were randomly assigned to 1 of 3 trial arms and received monthly treatment with (1) LMI alone, (2) cyclophosphamide followed 8 days later with LMI, or (3) the same treatment as in arm 2 with IL-2 given for 5 days beginning 1 week after LMI administration.
No grade 4 toxicities were observed. For patients with melanoma, median overall survival time for all 30 patients was 20.4 months [95% confidence interval (CI): 8.0-not assessable], and median progression-free survival was 2.8 months (95% CI: 1.9-6.3). For patients with RCC, median overall survival exceeded 46.2 months (95% CI: 30.3-not assessable), and median progression-free survival was 12.2 months (95% CI: 4.6-not assessable). Two patients had a partial response to LMI treatment.
Based on our results that demonstrate the safety and tolerability of LMI vaccine, further development of this therapy is warranted to evaluate its clinical efficacy.

1 Bookmark
 · 
114 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Active anti-cancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells (APCs). Therapy with autologous natural APCs is costly and time-consuming and results in variable outcomes in clinical trials. Therefore, development of artificial APCs (aAPCs) has attracted significant interest as an alternative. We discuss the characteristics of various types of acellular aAPCs, and their clinical potential in cancer immunotherapy. The size, shape, and ligand mobility of aAPCs and their presentation of different immunological signals can all have significant effects on cytotoxic T cell activation. Novel optimized aAPCs, combining carefully tuned properties, may lead to efficient immunomodulation and improved clinical responses in cancer immunotherapy.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Doelstelling: Er is hernieuwde interesse voor immunotherapie als behandeling voor gemetastaseerd niercelcarcinoom (NCC). Deze studie had als doel te bepalen of radiofrequente ablatie (RFA) gecombineerd met interleukine-2 (IL-2) een tumorspecifieke immuunrespons kan opwekken tegen NCC. Materiaal en methode: Muizen met getransplanteerde niertumoren werden behandeld met een combinatietherapie van RFA en IL-2, RFA of IL-2 als monotherapie, of geen behandeling (controle). De aanwezigheid van immunogene cellen in de primaire tumor werd bepaald door middel van immunohistochemie. In vitro cytotoxiciteit assays werden uitgevoerd met CD8+ T- en natural killer (NK) cellen uit de milt van behandelde muizen. Longmetastasen werden geïnduceerd door middel van intraveneuze injectie van tumorcellen voor of na de behandeling, waarna macroscopische longmetastasen werden gekwantificeerd. Resultaten: NK-, CD4+ en CD8+ T-cellen waren significant frequenter aanwezig in tumorweefsel van RFA/IL-2 behandelde muizen (p < 0,0001). Zowel NK- als CD8+ T-cellen uit de milt van de muis gaven een sterke antitumoractiviteit in vitro na behandeling met RFA/IL-2. Behandeling met RFA/ IL-2 gaf een significante preventie van longmetastasen (p < 0,0001). Bestaande longmetastasen waren kleiner in muizen die waren behandeld met RFA/IL-2 (p = 0,025) ten opzichtevan muizen die waren behandeld met IL-2. Conclusie: RFA van de primaire niertumor gecombineerd met IL-2 induceert een antitumoreffect tegen NCC dat veel sterker is dan het effect van IL-2 als monotherapie. Zowel NKals CD8+ T-cellen lijken een belangrijke rol te spelen bij dit effect. Deze therapie kan een belangrijke rol spelen in de ontwikkeling van nieuwe immunotherapeutische behandelingen voor NCC.
    10/2012; 2(6). DOI:10.1007/s13629-012-0064-7
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alkylating chemotherapy exerts both antineoplastic and immunostimulatory effects. However, in addition to depleting regulatory T cells (Treg), alkylating agents also mediate a long lasting antiproliferative effect on responder lymphocytes. Our recent findings indicate that this antiproliferative effect profoundly impairs vaccination-induced immune responses, especially in the case of vaccines that target specific tumor-associated neo-antigens that do not require Treg depletion.
    OncoImmunology 10/2013; 2(10):e26294. DOI:10.4161/onci.26294 · 6.28 Impact Factor