Biological and Molecular Factors Predicting Response to Adoptive Cell Therapies in Cancer

Author:

Ferrer Gerardo123ORCID,Álvarez-Errico Damiana13,Esteller Manel1345ORCID

Affiliation:

1. Cancer and Leukemia Epigenetics and Biology Program (PEBCL), Josep Carreras Leukaemia Research Institute (IJC), Badalona, Catalonia, Spain

2. Karches Center for Oncology Research, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA

3. Centro de Investigación Biomédica en Red Cáncer (CIBERONC) , Madrid, Madrid, Spain

4. Institució Catalana de Recerca i Estudis Avançats (ICREA) , Barcelona, Catalonia, Spain

5. Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB) , Barcelona, Catalonia, Spain

Abstract

AbstractAdoptive cell therapy (ACT) constitutes a major breakthrough in cancer management that has expanded in the past years due to impressive results showing durable and even curative responses for some patients with hematological malignancies. ACT leverages antigen specificity and cytotoxic mechanisms of the immune system, particularly relying on the patient’s T lymphocytes to target and eliminate malignant cells. This personalized therapeutic approach exemplifies the success of the joint effort of basic, translational, and clinical researchers that has turned the patient’s immune system into a great ally in the search for a cancer cure. ACTs are constantly improving to reach a maximum beneficial clinical response. Despite being very promising therapeutic options for certain types of cancers, mainly melanoma and hematological malignancies, these individualized treatments still present several shortcomings, including elevated costs, technical challenges, management of adverse side effects, and a limited population of responder patients. Thus, it is crucial to discover and develop reliable and robust biomarkers to specifically and sensitively pinpoint the patients that will benefit the most from ACT as well as those at higher risk of developing potentially serious toxicities. Although unique readouts of infused cell therapy success have not yet been identified, certain characteristics from the adoptive cells, the tumor, and/or the tumor microenvironment have been recognized to predict patients’ outcome on ACT. Here, we comment on the importance of biomarkers to predict ACT chances of success to maximize efficacy of treatments and increase patients’ survival.

Funder

Marie Skłodowska-Curie Action individual fellowship

CERCA Programme/Generalitat de Catalunya for institutional support

Health Department PERIS—project

AGAUR—project

Ministerio de Ciencia e Innovación

Agencia Estatal de Investigación (AEI) and European Regional Development Fund

Cellex Foundation

“la Caixa” Banking Foundation

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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