IO Networks

Lines of investigation:

CAR T cells for ALL B, ALL T, and AML. Normal and bispecific. Bi-specific and IMiDs in ALL and AML AML

Resources:

Platform NSG. MACS. FACS and sorter. Luminex

Protocols:

CAR T cells and xenogrfats (implant, management, treatment). Generation hybridoma and scFv

Needs:

Immunology studies

Lines of investigation:

1. Cell therapy and hematopoietic transplantation Immunomodulation and new drugs Cell therapy and transplantation Characterization of cells mesenchymal and its effect immunomodulator post-transplant
2. 2. New therapeutic targets Cell stem tumor
3. Mitochondrial function in myeloid pathologies Mouse mitochondrial dysfunction model AML.

Lines of investigation:

Biomarkers in Immune-oncology (biomarkers in tissue and blood); CSC and immune microenvironment

Resources:

Tumorspheres, Organoids, IHC, IF, NGSendez

Protocols:

TMB; -Luminex (analysis multiparametric): Soluble PDL-1, cytokines, chemokines,

Lines of investigation:

Characterization molecular and immune Cancer from lung microcytic and no microcytic as a basis for customizing immunotherapy strategies

Resources:

Sequencer Ion Torrent S5 XL, Sequencer Illumina NextSeq500, ultrasonicator COVARIS, core of immunohistochemistry (HRP, FISH), cytometers and sorters (core CNIO), Digital Droplet PCR (BioRad) with auto-droplet generator (robot automated), qPCR

Protocols:

Preparation from bookstores NGS (Illumina and Ion Torrent), disintegration from tumors cool to suspension cellular, separation from populations immune by FACS (sorting), marking by immunohistochemistry from tissue FFPE, marking and permeabilization from populations cell phones.

Needs:

Protocols from culture and expansion of TILs, protocols of NGS in biopsy liquid, IHC Multiplex, Bioinformatics

Lines of investigation:

Application of nanotechnology for the development of immunotherapies

Resources:

Optimization of nanosystems directed to tumor cells and / or immune cells of the tumor microenvironment, for therapeutic purposes.

Protocols:

Association of peptides, nucleic acids, proteins, antibodies, and other drugs, to nanosystems biocompatible and biodegradable, for the development of nano-immunotherapies

Needs:

In vitro and in vivo models for evaluation of the therapeutic potential of the nanosystems and proposed therapies.

Lines of investigation:

Interest in analysis of epigenetic biomarkers associated with immunotherapy

Resources:

Methylation analysis of genes with interest in immuno-oncology (EPIC arrays, NGS, pyrosequencing, MSP, qPCR, digital PCR, liquid biopsy)

Protocols:

Methylation analysis of genes with interest in immune-oncology

Needs:

Samples  of cancer patients  treated with immunotherapy to identify epigenetic biomarkers  of immunotherapy response

Lines of investigation:

CART therapy in clinical phase (CART19 in progress, CART-BCMA in preparation), CART therapy in pre-clinical phase (CD1a, CD123, HER2), TIL therapy in pre-clinical phase

Protocols:

Ongoing clinical trials with CART therapy. Production escalation protocols lentiviral(GMP). TIL protocols in preparation

Needs:

Improvements in the CAR sequence. Humanization of scFvs. Development of "safety-switch"novel (not patented). Optimization of production protocols. Development of new control strategies for the release syndrome cytokines.

Lines of investigation:

Redirect from T cells to tumors. Development and characterization of bispecific antibodies for the treatment of breast and colon cancer.

Resources:

Models from mice humanized by PBMCs

Models from mice humanized from cells parents CD34+.

Co-cultures of PBMCs and organoids (to depart of PDXs of Cancer breast, pancreas, gastric or colorectals).

Cytometry from flow for determination from populations immune in blood and intra-tumorous.

Protocols:

Generation of humanized mice, both with PBMCs and CD34 + progenitor cells, in patient derived xenograft (PDX) models. In vitro co-culture assays of PBMCs and tumor cells. Analysis of immune populations in disintegrated tumors. 

Needs:

Development of cells CAR T

Lines of investigation:

The Immune Landscape of the Stroma of Uterine Tumors; Extracellular Vesicles from Ewing Sarcoma and the formation of the Pre-Metastatic niche

Resources:

IHC, FACS, ELISA, biopsies liquid, NGS, nanostring

Protocols:

Isolation from platelets, isolation from vesicles extracellular from biopsy liquid, Nanostring

Needs:

Expertise specific in immuno-oncology in it area sarcomas / other tumors solid. The projects in this area they are relatively new.

Lines of investigation:

Cancer Colorectal - Establishment and development of humanized models of patient derived xenographs (PDX) for study of response to immunotherapy in combination with other targeted therapies. - Establishment and development of colonies and organoids of cancer colorectal - Characterization of the different molecular subtypes of cancer colorectal and relationship with the immune microenvironment and the antitumor response.

Resources:

Biobank from PDXs of colorectal cancer classified molecularly.

Unit of Cytometry flow

Genomics Unit

Protocols:

Protocols from establishment of PDXs. -  Protocols from isolation of PBMCs. -  Protocols of humanization through PBMCs.

Needs:

New approaches for the study of the tumor immune microenvironment and tumor response study in different preclinical models.

- Support in the development of specific protocols for other types of tumor, eg. breast and lung cancer.

- Collaborations in projects related to immune-oncology.

Lines of investigation:

Identification and validation of biomarkers through proteogenomics

Resources:

Methodology proteomics and nanotechnology

Protocols:

Proteomics and integration proteogenomics

Needs:

Samples from interest clinical/biological

Lines of investigation:

Ontogeny and classification of the immune response and its deficits

Resources:

Cytometry

Protocols:

Cytometry

Lines of investigation:

Study area: Immunology and Cancer (both with regard to the relationship between the immune system and cancer, as well as the study of neoplasms / clonal expansions derived from cells of the immune system and to the monitoring of the immune response after antitumor immunotherapy) Specific lines: 1.- Identification of aberrant protein expression patterns in hematological tumors and their use as markers of residual disease and for the identification of targets (immune) therapeutic. 2.- Design, development, standardization and validation of “Next Generation Flow cytometry Data ”for sensitive, fast and specific analysis of data from flow cytometry, applied to analysis immunophenotypic of hematological neoplasms. 3.- Design, development, standardization and validation of cytometry flow multiparametric (> 12 colors) of the latest generation for the identification of multiple populations of the immune system of functional relevance, for its application in the monitoring of the immune response after treatments immunotherapy (for example after antitumor immunotherapy).

Resources:

Post-immunotherapy immune response monitoring by multiparametric flow cytometry.

Monitoring of minimal residual disease through cytometry (in the case of hematological neoplasms).

Needs:

- Personnel training predoctoral and junior postdoctoral in functional trials additional to those performed in our group (eg ELISPOT technique).

- Training in molecular methods (especially NGS) applied to very scarce samples cellularity (<100 cells and <500 cells).

- Possibility of access to cell lines transfected in order to test anti-CD19 conjugated with fluorochrome to identify CART-cells

Lines of investigation:

Modulation of the complement system

Resources:

Syngeneic models of lung cancer

Protocols:

Functional assessment of suppressor myeloid cells, complement activation assessment protocols

Lines of investigation:

Leukocyte traffic through lymphatic vessels. Development of antitumor vaccines. Monoclonal Antibody Combinationsimmunostimulators. Cytokine-based tumor immunotherapy strategies. NK cell-based immunotherapy strategies.Radioimmunotherapy. Intravital microscopy. Adoptive cell therapy.

Resources:

Cytometers, luminometric camera in vivo, microPET, intravital microscopy, humanized models, 3D organoids

Protocols:

humanized models, 3D organoids

Needs:

Samples from patients

Lines of investigation:

Genetic and pharmacological strategies for the treatment of tumors with a mutation in the KRAS oncogene (lung cancer, pancreatic cancer and cholangiocarcinoma).

Mechanisms of resistance to targeted therapies.

Resources:

Genetics models of lung cancer, pancreatic cancer and cholangiocarcinoma.

Models of metastasis (intra-cardiac injection,, intra-venous)

Cytometers, luminometric camera for in vivo use, microPET, ecograph, organoids, microdissector.

Protocols:

Organoids (3D)

Needs:

Analysis of immune system in tumors primary from experimental  models and patients

Lines of investigation:

Evaluation of the immune component in the development and progression of cancer. Study of the tumor microenvironment.

Preclinical drug evaluation "immune check point inhibitors”In combination with compounds remodelers chromatin inhibitors or CDKs.

Study of the modification in the polarization of TAMs in tumor development and progression.

Effect of immunomodulatory compounds on cell activation NKs.

Evaluation of multivalent antibody fragments as directors of antitumor immune responses.

Resources:

Immunocompetent animals models genetically modified for preclinical evaluation.

Platforms for genomics studies (Nanostring, microarrays, NGS).

Samples collections from patients.

Protocols:

Generation and characterization of immunocompetent animal models.

Cellular characterization of tumors and biofluids by flow cytometry.

Genomic studies of mRNA gene expression and miRNAs (Microarrays, Nanostring)

NGS studies on platform Illumina.

Needs:

Study the methylation profiles of tumors and the effect of compounds remodelers of chromatin on the methylation of oncogenes.

3D Co-ccultures of tumor cells and stromal components (TAMs, CAFs, neutrophils)

Lines of investigation:

Molecular Biology of Sarcomas with translocations.

Resources:

NGS

Needs:

Bioinformatics

Lines of investigation:

Biopsy liquid

Tumorspheres

search of new drugs.

Resources:

Knowledge in some areas such as liquid biopsy or 3D cultures from patient samples.

Needs:

Application of knowledge and techniques in reference to IO.

Lines of investigation:

Molecular characterization of tumors and search for biomarkers and prognostic and predictive molecular profiles of response in various clinical scenarios (breast cancer, melanoma, colon, bladder, anus) through the use of omics techniques (NGS, genomics, proteomics and metabolomics) and computational analysis.

Resources:

From the Oncology translational lab, we can help in the processing and analysis of biological and clinical samples (cells, tissues, FFPE biopsies) using omics techniques: high-throughput (NGS, genomics, proteomics and metabolomics).

We have also established a computational analysis pipeline (probabilistic graphical models, classificatory algorithms, Flux balance analysis, preparation of predictors and differential expression analysis) with which we can provide a deeper molecular characterization of tumors and the interpretation of the data obtained from a systems biology perspective.

Needs:

Search for collaborations. Animal models of tumor disease and access to patient cohort samples for conducting studies.

Lines of investigation:

Cancer immunotherapy; melanoma; head and neck.

Resources:

Samples from patients.

Needs:

Learning in handling animal models and analysis techniques of biomarkers; collaborations in other projects to increase the sample size and be more competitive in European proposals.