The novel chelator lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA3-DTDA) promotes stable binding of His-tagged proteins to liposomal membranes: Potent anti-tumor responses induced by simultaneously targeting antigen, cytokine and costimulatory signals to T cells

AbstractRecent studies indicate that the chelator lipid nitrilotriacetic acid ditetradecylamine (NTA-DTDA) can be used to engraft T cell costimulatory molecules onto tumor cell membranes, potentially circumventing the need for genetic manipulation of the cells for development of cell- or membrane-based tumor vaccines. Here, we show that a related lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA3-DTDA, which has three NTA moieties in its headgroup instead of one) is several-fold more effective than NTA-DTDA at promoting stable His-tagged protein engraftment. IAsys biosensor studies show that binding of His-tagged B7.1 (B7.1-6H) to NTA3-DTDA-containing membranes, exhibit a faster on-rate and a slower off-rate, compared to membranes containing NTA-DTDA. Also, NTA3-DTDA-containing liposomes and plasma membrane vesicles (PMV) engrafted with B7.1-6H and CD40-6H exhibit greater binding to T cells, in vitro and in vivo. Engrafted NTA3-DTDA-containing PMV encapsulated cytokines such as IL-2, IL-12, GM-CSF and IFN-γ, allowing targeted delivery of both antigen and cytokine to T cells, and stimulation of antigen-specific T cell proliferation and cytotoxicity. Importantly, use of B7.1-CD40-engrafted PMV containing IL-2 and IL-12 as a vaccine in DBA/2J mice induced protection against challenge with syngeneic tumor cells (P815 mammary mastocytoma), and regression of established tumors. The results show that stable protein engraftment onto liposomal membranes using NTA3-DTDA can be used to simultaneously target associated antigen, costimulatory molecules and cytokines to T cells in vivo, inducing strong anti-tumor responses and immunotherapeutic effect

Conversações desassossegadas: diálogos sobre coleções etnográficas com o povo indígena Ka’apor

Este artigo trata do processo de diálogo sobre coleções etnográficas de objetos Ka’apor e da curadoria compartilhada da exposição “A Festa do Cauim”, atividades promovidas pelo Museu Nacional de Etnologia de Leiden (NME), Holanda, junto ao Museu Paraense Emílio Goeldi (MPEG), Brasil, e o povo indígena Ka’apor da Terra Indígena Alto Turiaçu, localizada no estado de Maranhão, na Amazônia brasileira. É reflexo de uma mudança de filosofia no NME em direção a uma atividade mais inclusiva e colaborativa, como também dos processos de atuação com povos indígenas promovidos no Museu Goeldi e da necessidade política dos Ka’apor de chamar atenção, em nível nacional e internacional, para a defesa de seus direitos territoriais, continuamente ameaçados por atores envolvidos com a exploração ilegal de madeira no seu território. Considerando diferentes enfoques disciplinares, principalmente da antropologia e da museologia, em consonância com o pensamento indígena, assim como com as negociações de interesses e encontro de diversas perspectivas cognitivas e posicionamentos políticos, este artigo, além de documentar e refletir sobre a produção cocriativa de uma exposição etnográfica, procura repensar as dimensões cognitiva, política e ética deste tipo de trabalho com povos indígenas. This article discusses the collaborative research and exhibition project Sharing Collections and Connecting Histories, carried out by the National Museum of Ethnology in Leiden (NME), the Netherlands, the Museu Paraense Emílio Goeldi, Brazil and the Ka’apor indigenous people of the indigenous reserve Alto Turiaçu, Maranhão, Brazil. The collaborative approach that characterized this project reflects a transformation that has been taking place at the NME in Leiden towards a more inclusive and collaborative museological work, and at the Museu Goeldi, which has been promoting collaborative work with indigenous peoples for at least two decades. The project seeks to meet the political needs of the Ka’apor to draw national and international attention to the importance of defending their territorial rights, which are continuously threatened by the illegal exploitation of lumber on their land. This article focuses on the dialogical processes of studying the Ka’apor collections and developing an exhibition. It considers different disciplinary foci — anthropology and museology — in dialogue with indigenous thought, as well as the process of negotiating the interests and the encounters between different cognitive perspectives and political positions. In addition to documenting and reflecting on the co-creative production of an ethnographic exhibition, this article reconsiders the cognitive, political and ethical dimensions of this type of work involving indigenous peoples