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OUTSOURCE

Financiado

Outsourcing cancer immunity to healthy donors

Despite recent advances in cancer immunotherapy, most patients with metastatic cancer are not cured. Major reasons are lack of homogeneously and highly expressed molecules that can be safely targeted and evoke efficient T-cell res... ver más

31/08/2025

Innovasjon Norge

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

Innovasjon Norge No se ha especificado una descripción o un objeto social para esta compañía.

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-06-04

ERC-2019-COG: ERC Consolidator Grant

I+D

Cerrada hace 5 años

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2 Participantes

Innovasjon Norge

2.00M€ | Lider

CALERAS DE LISKAR SA

227.16K€ | Participante

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Duración del proyecto: 62 meses Fecha Inicio: 2020-06-04
Fecha Fin: 2025-08-31

Líder del proyecto

Innovasjon Norge No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 2M€

Descripción del proyecto Despite recent advances in cancer immunotherapy, most patients with metastatic cancer are not cured. Major reasons are lack of homogeneously and highly expressed molecules that can be safely targeted and evoke efficient T-cell responses. I propose that the strong T-cell responses leading to rejection of transplanted organs can be exploited to reject cancer by specific recognition of tissue-restricted targets. To this end, I recently demonstrated that healthy donor blood provides a rich source of T cells expressing TCRs that specifically and strongly react to peptides from tissue-restricted self-proteins, when presented on mismatched, foreign Human Leukocyte Antigens (HLA). I propose that patient T cells genetically equipped with such donor TCRs (dTCR T cell therapy) may reject cancer-affected organs, including metastases. A high and homogeneous expression of tissue-specific antigens is often maintained on both primary tumor and metastatic cancer cells. Here, I will identify peptides from tissue-restricted proteins as novel candidate TCR targets. Next, I will identify donor T cells that recognize such self-peptides in complex with foreign HLA by use of my patented method, and sequence reactive TCRs. Finally, I will establish a preclinical pipeline to characterize safety and efficacy of TCRs in vitro and in vivo in innovative mouse models. Outsourcing cancer immunity to dTCR T cells may bypass major limitations in current immunotherapies, including checkpoint inhibition and T cells gene-modified with chimeric antigen receptors (CARs). Thus, dTCRs can recognize i) intracellular targets and thus manifold more targets than CARs, ii) tumor-associated self-antigens with high affinity in contrast to patient-derived TCRs, and iii) self-antigens, which are more homogeneously expressed than mutations. dTCR T cell therapy could treat malignancies in organs that are non-essential for survival, such as prostate, or that can be replaced by a transplant, such as bone marrow.

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