Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.

Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-γ signaling but did not require CD8+ T cell cytotoxicity. Cytokine-armed DCPs synergized effectively with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial gliomas in mice, illustrating their potential in combination therapies.

Allogeneic CAR T Cells: An Alternative to Overcome Challenges of CAR T Cell Therapy in Glioblastoma.

Chimeric antigen receptor (CAR) T cell therapy has emerged as one of the major breakthroughs in cancer immunotherapy in the last decade. Outstanding results in hematological malignancies and encouraging pre-clinical anti-tumor activity against a wide range of solid tumors have made CAR T cells one of the most promising fields for cancer therapies. CAR T cell therapy is currently being investigated in solid tumors including glioblastoma (GBM), a tumor for which survival has only modestly improved over the past decades. CAR T cells targeting EGFRvIII, Her2, or IL-13Rα2 have been tested in GBM, but the first clinical trials have shown modest results, potentially due to GBM heterogeneity and to the presence of an immunosuppressive microenvironment. Until now, the use of autologous T cells to manufacture CAR products has been the norm, but this approach has several disadvantages regarding production time, cost, manufacturing delay and dependence on functional fitness of patient T cells, often reduced by the disease or previous therapies. Universal "off-the-shelf," or allogeneic, CAR T cells is an alternative that can potentially overcome these issues, and allow for multiple modifications and CAR combinations to target multiple tumor antigens and avoid tumor escape. Advances in genome editing tools, especially via CRISPR/Cas9, might allow overcoming the two main limitations of allogeneic CAR T cells product, i.e., graft-vs.-host disease and host allorejection. Here, we will discuss how allogeneic CAR T cells could allow for multivalent approaches and alteration of the tumor microenvironment, potentially allowing the development of next generation therapies for the treatment of patients with GBM.

Visualización de liposomas por resonancia magnética: una oportunidad para mejorar las terapias liposomales antitumorales / Visualization of liposomes by magnetic resonance imaging: an opportunity to improve antitumoral liposome therapies

La liberación controlada de fármacos en el sitio del tumor y el desarrollo de técnicas no invasivas de monitoreo constituyen 2 de los principales retos que enfrentan las terapias antitumorales en la actualidad. En este trabajo se analizan algunas de las potencialidades del uso de liposomas como vehículos para el transporte de drogas hasta los tumores, especialmente de las variantes direccionalizadas a antígenos tumorales mediante el acoplamiento de anticuerpos (inmunoliposomas). Estas vesículas pueden a su vez ser utilizadas en combinación con el uso de imágenes de resonancia magnética, una de las técnicas de imagenología más utilizadas y de mayores potencialidades en la visualización a nivel molecular. El uso conjunto de estas 2 tecnologías permite controlar la cantidad de fármaco administrado, así como predecir la eficacia del tratamiento y monitorear la progresión de este

Controlled release of drugs at the tumor site and the development of non-invasive monitoring techniques are two of the main challenges currently facing antitumoral therapies. The paper analyzes some of the potential uses of liposomes as vehicles for the transport of drugs to the tumors, particularly directionalized variants to tumor antigens through antibody coupling (immunoliposomes). These vesicles may also be used in combination with magnetic resonance, one of the most widely used imaging techniques, and one exhibiting great visualization potential at molecular level. Joint use of these two techniques makes it possible to control the amount of drug administered, as well as predict the efficacy of the treatment and monitor its progress