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Cell Vaccination (cell + vaccination)
Selected AbstractsAntigen co-encapsulated with adjuvants efficiently drive protective T cell immunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Antje Heit Abstract Compared to "live" vaccines, the immunogenicity of "subunit" vaccines based on recombinant antigen (Ag) is poor, presumably because exogenous Ag fails to effectively access the endosomal Ag-processing pathways of Ag-presenting cells (APC). To overcome this limitation, we exploited biodegradable poly(lactic-co-glycolic) microspheres (MP) co-entrapping Ag and Toll-like receptor (TLR) 9 or 7 ligands as an endosomal delivery device. In vitro, microspheres were rapidly phagocytosed by APC and translocated into phago-endosomal compartments, followed by degradation of the Ag and concurrent activation of endosomal TLR. As a consequence, full maturation of and cytokine secretion by APC as well as Ag-cross-presentation ensued. In vivo, "loaded" microspheres triggered clonal expansion of primary and secondary Ag-specific CD4 and CD8 T cells. The efficacy of CD8 T cell cross-priming was comparable to that of live vectors. The potency of T cell vaccination was demonstrated by protective and therapeutic interventions using infection- and tumor-model systems. These preclinical "subunit" vaccination data thus recommend MP as a generally applicable and powerful endosomal delivery device of exogenous Ag plus TLR-based adjuvants to vaccinate for protective and therapeutic CD4 and CD8 T cell immunity. [source] Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experienceINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2002Takeshi Azuma Abstract Background : Dendritic cells (DC) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed. Methods : Dendritic cells were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte,macrophage colony-stimulating factor and interleukin-4. On day 6 the DC were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-pulsed DC by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were, respectively, evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. Results : Three patients were enrolled and the immunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. Clinical responses consisted of one case of no change and two cases of progression of disease. However, we did not see a significant reduction of tumor volume in any case. Conclusion : Dendritic cell vaccination can safely induce an immunological response against RCC. Further trials are needed to fully evaluate its efficacy. [source] Dendritic cell vaccination and immune monitoringISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue 1 2009E. H. J. G. Aarntzen Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. Following infection or inflammation, they undergo a complex process of maturation and migrate to lymph nodes where they present antigens to T cells. Their decisive role in inducing immunity formed the rationale for DC immunotherapy: DCs loaded with tumour antigens are injected into cancer patients to stimulate T cells to eradicate tumours. Effective immune responses and favourable clinical outcomes have indeed been observed, but only in a minority of patients. Therefore, it is obvious that current DC-based protocols need to be improved. For this reason, we study in small proof-of-principle trials the fate, interactions and effectiveness of the injected DC. The success of DC-based immunotherapy to induce cellular immunity against tumours is highly dependent on accurate delivery and trafficking of the DC to T cell-rich areas of secondary lymphoid tissues. [source] Vaccination with selected synovial T cells in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 2 2007Guangjie Chen Objective This pilot clinical study was undertaken to investigate the role of T cell vaccination in the induction of regulatory immune responses in patients with rheumatoid arthritis (RA). Methods Autologous synovial T cells were selected for pathologic relevance, rendered inactive by irradiation, and used for vaccination. Fifteen patients received T cell vaccination via 6 subcutaneous inoculations over a period of 12 months. Results T cell vaccination led to induction of CD4+ Tregs and CD8+ cytotoxic T cells specific for T cell vaccine. There was selective expansion of CD4+,V,2+ Tregs that produced interleukin-10 (IL-10) and expressed a high level of transcription factor Foxp3, which coincided with depletion of overexpressed BV14+ T cells in treated patients. CD4+ IL-10,secreting Tregs induced by T cell vaccination were found to react specifically with peptides derived from IL-2 receptor ,-chain. The expression level of Foxp3 in CD4+ T cells and increased inhibitory activity of CD4+,CD25+ Tregs were significantly elevated following T cell vaccination. The observed regulatory immune responses collectively correlated with clinical improvement in treated patients. In an intent-to-treat analysis, a substantial response, defined as meeting the American College of Rheumatology 50% improvement criteria, was shown in 10 of the 15 patients (66.7%) and was accompanied by a marked improvement in RA-related laboratory parameters. Conclusion These findings suggest that T cell vaccination induces regulatory immune responses that are associated with improved clinical and laboratory variables in RA patients. [source] Phase I/II clinical trial of sequential subcutaneous and intravenous delivery of dendritic cell vaccination for refractory multiple myeloma using patient-specific tumour idiotype protein or idiotype (VDJ)-derived class I-restricted peptidesBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2007Antonio Curti Summary Fifteen multiple myeloma (MM) patients who had failed maintenance therapy after tandem autologous stem cell transplantation underwent anti-idiotype (Id) vaccination with dendritic cells (DCs). CD14+ -derived DCs were loaded with the autologous Id as whole protein (=6) or Id-derived class I-restricted peptides (=9) and keyhole limpet hemocyanin (KLH). Vaccination consisted of three subcutaneous (sc) and two intravenous injections of increasing DC doses at 2 weeks interval. DC therapy was well tolerated. Most patients developed both humoral and T-cell responses to KLH, suggesting immunocompetence. Eight of 15 patients developed an Id-specific T-cell proliferative response, 8/15 increased interferon-,-secreting T cells and 4/15 showed an Id-positive delayed-type hypersensitivity test. Anti-Id cytotoxic T-lymphocyte precursors increased after DC vaccination in 2/2 evaluable patients. A more robust T-cell response was observed after sc DC injections and increased Id-specific T-cell proliferation was found up to 1 year after vaccination. VDJ-derived peptides were as effective as the whole protein in stimulating T-cell responses. Clinically, 7/15 patients have stable disease after a median follow-up of 26 months, one patient achieved durable partial remission after 40 months, and seven patients progressed. In conclusion, sc injections of cryopreserved Id-pulsed DCs were safe and, in contrast with intravenous administrations, induced anti-MM T-cell responses. [source] Making use of the primary tumourBIOESSAYS, Issue 1 2003Arnold Baars Surgical resection of a primary tumour is often not sufficient to cure a patient. Even when no residual cancer can be detected at time of surgery, metastases may appear in the following years, which indicates that the primary tumour had apparently spread before surgery. Following surgery, systemic chemotherapy may be used to eradicate micro-metastatic disease. Here we present two unconventional strategies that implement new insights into tumour biology and tumour immunology in the treatment of patients with cancer. Both experimental strategies use the individual characteristics of the patient's primary tumour to optimise the control of life-threatening micro-metastases. We aim to modulate the patient's adaptive immune system, targeting it towards the patient's own tumour cells to eradicate residual disease following local treatment. In one approach, this is done by autologous tumour cell vaccinations as adjuvant treatment for colon cancer patients and, in a second approach, by giving chemo-imunotherapy before local treatment to women with locally advanced breast cancer. BioEssays 25:79,86, 2003. © 2002 Wiley Periodicals, Inc. [source] | ||||||||||