Rebeca Parracho

Experience

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  Champalimaud Foundation

  Jan 2021 - Jun 2021

  PROJECT IN CELL AND MOLECULAR BIOLOGY | ImmunoTherapy/ImmunoSurgery Lab

  Project Title: Tumour Infiltrating Lymphocytes in Cellular Immunotherapy and their reactivity towards different stimuliAbstract: Tumour infiltrating lymphocytes (TILs) are a heterogeneous group of immune cells, and those grown from tumours and cultured in vitro consist majorly of CD8+ and CD4+ T-cells. Adoptive cell therapy (ACT) using TILs has been more and more used successfully in treating patients with diverse cancer indications besides malignant melanoma, as they mimic the behaviours of pre-existent immune cells and are programmed for long-term persistence and enhanced effector functions.Intact full-length IgG antibodies fused to immunostimulatory cytokines combine the specificity for tumour markers with the power to orchestrate immune responses which lead to proliferation, differentiation, effector functions, and survival of leucocytes. Several Interleukin-Antibody fusion proteins have strong indications of being an effective alternative to antitumoral therapy, as it enhances direct antitumour activity and elicits a secondary humoral and/or cell-mediated immune response, all while simultaneously avoiding undesired complications or systemic toxicity.Assessing the potential synergistic activity of monofunctional single cytokine–antibody fusion proteins can help discover the optimal stimulatory cocktail that augments TIL growth and function in vitro, subsequently improving ACT efficacy.The data shows how heterogeneity and small numbered sample influence what we obtained, being only possible to propose that the cytokine cocktail IL-7, IL-15, and IL- 21 conjugated with IgG1 is most likely the best candidate to achieve what is intended.Hence, this project serves as a starting point for further optimization of methods aiming to define a preferred standard TIL expansion protocol.Final Grade: 19 out of 20 Show less

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  SciLifeLab

  Nov 2021 - Jan 2022

  CURRICULAR RESEARCH PROJECT | Science for Life Laboratory

  Project in Advanced Techniques in Molecular Medicine at Molecular Epidemiology and Translational Medicine Lab. The aim of the research work was to systematically identify and characterize causal genes for cardiovascular and metabolic diseases in order to reduce the large number of GWAS-based candidate genes to a more feasible number for in-depth characterization, improving our understanding of disease etiology and possibly identify novel targets for prevention and treatment.Grade: Pass with credit (4) Show less

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  Uppsala University, Department of Immunology, Genetics and Pathology

  Oct 2022 - Jun 2023

  Master Thesis Project

  Thesis title: Mechanistic investigation of immune checkpoint blockade therapy: Unveiling the potential of next-generation immune checkpoint LAG-3 in cancerAbstract: Immune checkpoint inhibitors (ICB) have revolutionized the field of ‘immuno-oncology’, yet many patients fail to enjoy long-term benefits due to several intrinsic resistance features of the solid tumour microenvironment. Recently, a combination therapy involving the blockade of lymphocyte-activation gene 3 (LAG-3) and programmed-death 1 (PD-1) was approved as first-line treatment for metastatic/unresectable melanoma. However, several relevant questions regarding this dual blockade therapy remain unaddressed, including its effects on different immune cell populations and the underlying synergistic mechanisms between LAG-3 and other immune checkpoints.To address this, the project focused on the development of a complex tumour-immune cell co-culture (TICS) assay to investigate the dynamic interplay between the human immune system and cancer cells in response to ICB, with emphasis on LAG-3 blockade-induced immune activation.Using triple negative breast cancer (MDA-MB-231) and PD-1 blockade-resistant melanoma (M464) cell lines, results indicated that single blockade of LAG-3 had no impact or seemingly inhibitory effects on the immune response. Interestingly, the combination of LAG-3 and PD-1 or PD-L1 blockade exhibited differential effects on lymphocyte activation in TICS. Notably, a suggestive synergistic effect was observed in the proliferation of natural killer (NK) cells and CD4+ T-cells.Together, these findings emphasise the potential of LAG-3 being a worthy target in cancer immunotherapy. Nonetheless, further investigations are warranted to fully elucidate the mechanistic basis of combined LAG-3 blockade.Final Grade: VGAcknowledgment of the privilege it was to work within Yumeng Mao's Research Group in Clinical Cancer Immunology. Show less

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  Uppsala University, Department of Immunology, Genetics and Pathology

  Aug 2023 - now

  Research Intern