Vaccine Development

"Our research in the development of dendritic cell-based vaccines has resulted in different vaccination protocols that have been tested in patients."

DR. PABLO SAROBE UGARRIZA
RESEARCHER. VACCINE DEVELOPMENT RESEARCH GROUP

Cima's Vaccine Development Research Group focuses on the development of vaccines based on the modulation of dendritic cells (DCs), a type of antigen-presenting immune cells responsible for detecting pathogens and presenting their antigens to T lymphocytes (LTs), which will develop their effector functions.

For proper LT activation, DCs are required to undergo a maturation process that involves increased expression of antigen presenting molecules (MHC), co-stimuli, as well as LT polarizing cytokines. DC maturation occurs as a consequence of the recognition of pathogen-associated molecules or danger signals. The characterization of these molecules, their corresponding receptors on DCs, as well as the signaling pathways involved in these processes, has allowed us to advance in the knowledge of DC biology and in the development of new vaccination strategies.

Our group is investigating the use of different molecules that favor DC maturation, combinations between them, as well as with antigens of interest in cancer, mainly in hepatocarcinoma, to develop more potent vaccination strategies.

It is known that DC maturation is accompanied by autoregulatory mechanisms that modulate their activity so that it does not reach levels that exacerbate the response, becoming harmful. In certain situations, such as cancer, these mechanisms are over-expressed, leading to deficient activity of this cell population. In this sense, we are working on enhancing the activity of DCs by blocking or inhibiting these immunosuppressive mechanisms.

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Vaccine Development Research Group Objectives

We seek to enhance immunotherapy treatments through cross-cutting research

Characterization of the basic mechanisms of immune response activation.

Design of new vaccination strategies.

Development of vaccines for oncological and viral diseases.

TRANSLATIONAL RESEARCH

Cytokines in clinical cancer immunotherapy

The antitumor properties of cytokines have led to an exponential increase in the number of research and clinical trials exploring the safety and efficacy of cytokine-based drugs, not only as single agents but also in combination with other immunomodulatory drugs.

These new trends in the field of cytokine immunotherapy are producing promising therapeutic agents and the design of new strategies with potential clinical application, such as anti-TNF therapy.

Research lines in Vaccine Development

IPs: Pablo Sarobe y Sandra Hervás

Aunque la mayoría los pacientes tienen una respuesta inmunitaria específica para su cáncer, las células cancerosas encuentran formas de evadir la vigilancia inmunológica. Las Inmunoterapias basadas en los bloqueantes de los conocidos inmunocheckpoint han mostrado efectos positivos en una proporción significativa de pacientes. Desafortunadamente, en la mayoría de los casos, estas terapias inmunomoduladoras no son curativas por la ausencia de una respuesta inmunitaria preexistente.

En este escenario, la identificación de antígenos tumorales específicos para el desarrollo de vacunas han sido objeto de una intensa investigación. El increíble progreso en las técnicas de secuenciación (NGS) está haciendo posible la identificación de antígenos tumorales únicos para el diseño y fabricación de vacunas personalizadas frente a diferentes tipos de tumores. En el laboratorio hemos trabajado en el desarrollo de un pipeline para la identificación de mutaciones y neoantígenos a partir de muestras de pacientes, con el objetivo de poder incorporarlos en formulaciones basadas en péptidos sintéticos o en ARN/ADN para el diseño de vacunas personalizadas.

Objetivos:

Identificar antígenos para la selección de linfocitos T específicos de tumor.
Identificar mutaciones en tumores hepáticos (hepatocarcinoma; HCC) y en cáncer mama triple negativo.
Identificar neo-antígenos para ser incluidos en vacunas personalizadas.
Estudiar la eficacia de la combinación de vacunas con agentes inmunomoduladores (checkpoint inhibitors, drogas epigenéticas y otros).

Realizamos esta investigación en colaboración con la Unidad del Hepatología (Dr. Bruno Sangro) y con el Departamento de Oncología (Dra Marta Santisteban) de la Clínica Universidad de Navarra.

PI: Ignacio Melero

We are working on the study of the role of dendritic cells (DCs) in crosspriming for the induction of effective cellular responses. The manipulation of DCs for cancer vaccination has not reached its full potential, despite the revolution in cancer immunotherapy. DCs are essential for the activation of CD8+ T cells, which rely on cross-presentation of exogenous antigens at MHC-I and can be promoted by immunogenic cancer cell death. For this reason, it is important to delve into the mechanisms and cells that are capable of cross-presentation of tumor antigens that more effectively promote the activation of antitumor immune responses.

Objectives:

To study the mechanisms of tumor antigen cross-priming and its requirement in immunotherapy.
To generate a clinical grade system for immunomagnetic isolation of the dendritic cell population that mediates crosspriming.
To perform two proof-of-concept clinical trials using anti-tumor vaccination with crosspriming-mediated dendritic cells in patients with ovarian and prostate cancer.

PIs: Pablo Sarobe y Juan José Lasarte

In the context of the pandemic caused by the SARS-Cov-2 virus, and the social alarm generated, we considered it necessary to apply our knowledge to the study of the immunogenicity of the virus and to evaluate the possibility of developing a vaccine based on synthetic peptides derived from viral proteins. Preliminary results allow us to confirm that it is possible to induce neutralizing antibodies using specific peptide sequences of the virus. We intend to continue this work and analyze its possible usefulness against new variants of the virus.

Objectives:

Continue with the identification of immunogenic regions in SARS-CoV-2 proteins for the development of peptide-based vaccines.
Evaluation of their immunogenicity and their capacity to induce neutralizing responses.