487 research outputs found
A kinetic investigation of interacting, stimulated T cells identifies conditions for rapid functional enhancement, minimal phenotype differentiation, and improved adoptive cell transfer tumor eradication.
No full textFor adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an effective therapeutic outcome depends upon cell dose, cell expansion in vivo through a minimally differentiated phenotype, long term persistence, and strong cytolytic effector function. An incomplete understanding of the biological coupling between T cell expansion, differentiation, and response to stimulation hinders the co-optimization of these factors. We report on a biophysical investigation of how the short-term kinetics of T cell functional activation, through molecular stimulation and cell-cell interactions, competes with phenotype differentiation. T cells receive molecular stimulation for a few minutes to a few hours in bulk culture. Following this priming period, the cells are then analyzed at the transcriptional level, or isolated as single cells, with continuing molecular stimulation, within microchambers for analysis via 11-plex secreted protein assays. We resolve a rapid feedback mechanism, promoted by T cell-T cell contact interactions, which strongly amplifies T cell functional performance while yielding only minimal phenotype differentiation. When tested in mouse models of ACT, optimally primed T cells lead to complete tumor eradication. A similar kinetic process is identified in CD8+ and CD4+ T cells collected from a patient with metastatic melanoma
sj-docx-1-pcr-10.1177_26323524231225249 – Supplemental material for Improving shared decision-making about cancer treatment through design-based data-driven decision-support tools and redesigning care paths: an overview of the 4D PICTURE project
No full textSupplemental material, sj-docx-1-pcr-10.1177_26323524231225249 for Improving shared decision-making about cancer treatment through design-based data-driven decision-support tools and redesigning care paths: an overview of the 4D PICTURE project by Judith A. C. Rietjens, Ingeborg Griffioen, Jorge Sierra-Pérez, Gaby Sroczynski, Uwe Siebert, Alena Buyx, Barbara Peric, Inge Marie Svane, Jasper B. P. Brands, Karina D. Steffensen, Carlos Romero Piqueras, Elham Hedayati, Maria M. Karsten, Norbert Couespel, Canan Akoglu, Roberto Pazo-Cid, Paul Rayson, Hester F. Lingsma, Maartje H. N. Schermer, Ewout W. Steyerberg, Sheila A. Payne, Ida J. Korfage and Anne M. Stiggelbout in Palliative Care and Social Practice</p
Analysis of Survivin-Specific T Cells in Breast Cancer Patients Using Human DCs Engineered with Survivin mRNA
No full textThe observation that dendritic cells (DCs) charged with tumor-associated antigens (TAAs) is a potent strategy to elicit protective immunity in tumor-bearings hosts has prompted extensive testing of DCs as cellular adjuvant in cancer vaccines. To improve the clinical development of DC-based cancer vaccines, it may be beneficial to analyze preexistent immunity against TAAs in cancer patients because it may be easier to expand a memory pool of T cells compared to generating new immunity. Recent research shows that engineering DCs to synthesize tumor epitopes endogenously by transfecting DCs with mRNA-encoding TAAs are particular effective in stimulating robust T-responses in vitro and in vivo. In this chapter, we describe the methodology to analyze for survivin-specific T cells in breast cancer patients using human DCs engineered with survivin mRNA
Comment on "Adoptive T-cell therapy for malignant melanoma patients with TILs obtained by ultrasound-guided needle biopsy" by Gustav J. Ullenhag et al
No full textHarnessing neoantigen-specific T cells for precision cancer immunotherapy
No full textSeveral novel personalized therapies focus on targeting neoantigens. Such strategies require the identification of suitable vaccine neoepitopes or neoantigen-specific T cell receptor (TCR) clonotypes. Herein, we discuss a recently published report that describes a combined transcriptional and phenotype signature, NeoTCRPBL, that enables the minimally invasive identification of rare neoantigen-specific TCRs from peripheral blood that might enable more-effective T cell-based therapies against cancer.</p
Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma:what is needed to achieve standard of care?
No full textAdoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh tumor tissues after ex vivo activation and extensive expansion. TIL-based ACT has so far only been tested in smaller phase I/II studies, but these studies consistently confirm an impressive clinical response rate of up to 50 % in metastatic melanoma including a significant proportion of patients with durable complete tumor eradication. These remarkable results justify the need for a definitive phase III trial documenting the efficacy of this type of T cell-based Advanced Therapy Medicinal Product in order to pave the way for regulatory approval and implementation of TIL therapy as a new treatment standard in oncology practice. TIL-based ACT can, however, only be offered to a limited group of patients based on the need for accessible tumor tissue, the complexity of TIL production procedures, and the very intensive nature of this three-step treatment including both high-dose chemotherapy and interleukin-2 in addition to T cell infusion. To this end, adoptive T cell therapy using peripheral blood mononuclear cell-derived T cells could be a welcome alternative to circumvent these limitations and broaden up the applicability of ACT. Here, we discuss current initiatives in this focused research review.</p
Animal bones from the Ronæs Skov settlement
No full textAnalyser af dyreknogler fra en submarin boplads, Ronæs Skov, ved Gamborg Fjord på Fyn, påviser mindst syv arter af fisk, fire arter af fugle og nitten arter af pattedyr. Fiskeriet har især været domineret af torsk. Fuglefangsten har bestået af skarv, svane, spurvehøg og natugle. Foruden den for perioden karakterisktiske jagt på vildsvin, kronhjort og rådyr har der foregået en vis hvalfangst. Det er interessant, at der er fanget marsvin, som der også i nutiden har været drevet storjagt på i dette områdeAnalyses of animal bones excavated on a submarine stone Age settlement, Ronæs Skov, at Gamborg Fjord, Funen. At least seven species of fish, four species of birds and nineteen species of mammals were exploited at this Ertebølle site. Fishing for cod were characteristic and swans as well as cormorants were hunted. The most frequent mammals at the site in the Ronæs skov material are wild boar, red deer and roe deer. A significant element of marine mammals is also apparant: several species of seal and whale. Especially bones from harboar porpoise are worth noting
Immune monitoring using mRNA-transfected dendritic cells
No full textDendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by mRNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA.</p
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