Platform for the Identification of Tumor Antigen-Specific TCRs for Solid Tumor Immunosorbent Assay

The PITAGORAS project seeks to develop a platform for the identification of tumor antigen-specific TCRs for immunotherapy of solid tumors.

The TCR is the natural receptor on T cells that allows them to recognize foreign cells, such as tumor cells. Therapy with T cells genetically modified to express these receptors (TCR-T cells) is a new cell therapy modality for cancer treatment. The great advantage of this therapy over related therapies, such as CAR-T therapy, is the abundance of tumor antigens that are intracellular and therefore can only be recognized by the TCR. This is of vital importance in the context of solid tumors, where the lack of good antigens for CAR-T cells is limiting their efficacy. 

There are currently two approaches to TCR-T therapies: with "shared TCRs", which recognize tumor antigens shared by different patients; and with "personalized TCRs", which recognize the patient's own tumor antigens, the most frequent. The challenges differ for both approaches: while shared TCRs require solutions that facilitate their implementation in clinical practice, personalized TCRs need simple methods to identify tumor-specific TCRs and thus make their way into personalized medicine. At PITAGORAS we address both challenges.

Taking as a starting point "shared TCRs" specific to human tumor antigens identified by FIMA, we propose to establish protocols for clinical-scale production of TCR-T cells to facilitate their translation to the clinic. On the other hand, in order to propose improved versions of TCRs and combination treatments that enhance TCR-T therapy, we will study the molecular structure of these TCRs, their interaction with tumor cells, by image analysis and using in vitro and in vivo models in zebrafish, as well as the mechanisms of tumor resistance to attack by TCR-T cells. For the development of "personalized TCR" therapies, we propose to develop a rapid and novel method to identify tumor-specific TCRs using next-generation sequencing (NGS) data and the genetic profile of T lymphocytes. 

It is funded by the Government of Navarra within its call for Strategic R&D Projects 2023.

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Coordinator and partners

Project coordinator: 

  • The Fundación para la Investigación Médica Aplicada (FIMA)

Project partners:

  • Clínica Universidad de Navarra
  • Navarrabiomed (Nbio)
  • Navarra Hospital Complex (HUN)
  • IKAN Biotech
  • 3P Biopharmaceuticals (3P bio)
  • ADItech

PITAGORAS project objectives

Establish a platform for the identification and development of TCRs for use in adoptive cell therapy (ACT) of solid tumors.

Identify tumor-specific TCRs

based on the transcriptomic signature of TILs for the development of personalized TCR therapies.

Development of candidate TCR

We will focus on GPC3 TCRs, for their optimization and to facilitate their translation to the clinic.

Icono equipo profesionales PITAGORAS project participants

  • Sandra Hervás
  • Uxua Mancheño
  • María Antonia Fortuño
  • Virginia Villar
  • Patxi San Martín
  • Sarai Sarvide
  • Mikel Hernáez
  • Ibon Tamayo
  • Juan José Lasarte
  • Diana Isabel Llopiz
  • Marta Ruiz
  • Maritza Roxana García
  • Carlos Ortiz de Solórzano
  • Lucía Grande
  • Iván Cortés
  • Juan Dubrot
  • María Cristina Sainz
  • Antonio Ángel Pineda
  • Eva Molina
  • Diego Sergio Medarde
  • Ascensión López-Díaz de Cerio
  • Susana Inogés
  • Margarita Legarrea
  • Rebeca Lara
  • Leire Garate
  • Rodrigo Redondo
  • Maider Garnica
  • Enrique Conde
  • Laura Álvarez
  • Marta Abengózar
  • Bruno Sangro
  • Josep María Argemi
  • José Ángel Mínguez
  • Enrique María Chacón
  • Ángel Vizcay
  • José Manuel Aramendía
  • Rafael Salido
  • Miguel Fernández

  • Jacinto López 
  • Gilda Dichiara
  • Elena Erausquin
  • Juan Carlos Muruzábal
  • Rosa Guarch
  • Nadia Veiga
  • María Pilar Fernández
  • Gonzalo Rodríguez
  • Ibai Goicoechea
  • Iranzu Lamberto
  • Jorge Jiménez
  • Cristina García
  • Susana Pascoal
  • Jairo Pérez
  • Eva Martisovà
  • Beatriz Marcos
  • Natalia Aguado
  • Elena Sánchez
  • Ana Azcárate
  • Olga Morejón
  • Carlos López
  • David Villanueva
  • Íñigo Sarobe
  • Andrés Guerrero
  •    María Andrea Dellafiore 
  • Laura Saludas
  • Eider Orradre 
  • María Uresandi
  • Jon Izaguirre
  • Gonzalo Eciolaza

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