Promising tests in cancer immunotherapy

A novel immunotherapy to fight cancer

(UCLouvain press release)

Sophie Lucas, researcher at the de Duve at UCLouvain, and her team succeeded in neutralizing a molecule that blocks immune responses against cancer. The UCLouvain scientists discovered that this novel form of immunotherapy induces tumor regressions by strongly increasing the efficacy of another well-known immunotherapeutic approach. Their discovery, very promising for the fight against cancer, is published in the prestigious scientific journal Nature Communications.

Cancer immunotherapy consists in manipulating immune cells in patients to fight cancer. The specificity of immunotherapy is to stimulate or boost healthy immune cells in the human body, so these cells can in turn kill the cancer cells that form the tumor. Often indeed, anti-tumor immune defenses are paralyzed by cells or molecules that prevent immune cells from killing cancer cells, allowing the tumor to settle and grow.

In 2004, Sophie Lucas, now president of the de Duve Institute at UCLouvain, decided to tackle the following question: “How are anti-tumor immune responses blocked in cancer patients?”. More precisely, she wanted to understand how a very special type of cells called Regulatory T lymphocytes, or Tregs, exert potent “immunosuppression” within tumors. In 2009, the young UCLouvain researcher discovered GARP, a molecule located on the surface of Tregs.

In 2018, Sophie Lucas finally managed to understand the role of GARP: the molecule acts as a messenger for Tregs, by sending inhibitory signals that block immune defenses. She then developed a tool (anti-GARP antibodies) to neutralize the inhibitory messenger and prevent it from sending its paralyzing signal. This important discovery was published in Science. It allowed the team to propose using anti-GARP antibodies as a new immunotherapeutic agent (a new drug) against cancer.

August 2020. Nature Communications publishes the results of the first tests carried out by Sophie Lucas and her team to evaluate the new drug. Their conclusions are very promising: the scientists succeeded in neutralizing Tregs in tumor-bearing mice using anti-GARP antibodies. When the inhibitory messenger was neutralized, anti-tumor immune responses were no longer paralyzed and started to eliminate cancer cells. The result? Tumors regressed quickly, provided that the anti-GARP antibodies were combined with another immunotherapy (so-called PD1 blockade proven to work in patients. The bet of Sophie Lucas' team? Combine the two complementary immunotherapies, which act on distinct pathways of the immune system, to increase the efficacy of treatments against cancer. And it worked!

What will happen next? Similar tests will be carried out in cancer patients, with the hope to provide a more effective therapy against cancer.

Tregs expressing GARP are found in human melanoma samples.

Article describing this research

Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer

de Streel G, Bertrand C, Chalon N, Liénart S, Bricard O, Lecomte S, Devreux J, Gaignage M, De Boeck G, Mariën L, Van De Walle I, van der Woning B, Saunders M, de Haard H, Vermeersch E, Maes W, Deckmyn H, Coulie PG, van Baren N and Lucas S

Nat. Commun. (2020) 11:45

In the press

Cordis.europa.eu - Unblocking the body’s natural defence against cancer - 8/10/2021

ScienceBoard.net - New approach to cancer immunotherapies combines 2 mAb treatments - 11/09/2020

MedicalXpress.com - New immunotherapy to beat cancer - 11/09/2020

News-Medical.net - Combined immunotherapy approaches increase the effectiveness of cancer treatment - 11/09/2020

HomeHealthChoices.com - New immunotherapy to beat most cancers - 11/09/2020

ScienceOwl.co.uk - A new method to enhance cancer treatment - 18/09/2020

CardiffStudentMedia.co.uk - Potential immunotherapy effective against cancer - 29/09/2020

Cordis.europa.eu - Débloquer la défense naturelle de l’organisme contre le cancer - 8/10/2021

BX1.be - Des chercheurs de l’UCLouvain ont découvert une nouvelle immunothérapie pour vaincre le cancer (video) - 11/09/2020

RTBF.be - Nouvelle Immunothérapie dans la lutte contre le cancer (video) - 19/09/2020

LeSoir.be - Une nouvelle immunothérapie contre le cancer - 11/09/2020

RTBF.be - Des chercheurs de l'UCLouvain mettent au point une immunothérapie plus performante contre le cancer - 11/09/2020

7sur7.be - L'UCLouvain fait une découverte prometteuse pour faire régresser les tumeurs cancéreuses - 11/09/2020

Medi-Sphere.be - Des chercheurs de l’UCLouvain font une découverte prometteuse contre le cancer - 11/09/2020

MyScience.be - Nouvelle immunothérapie pour vaincre le cancer - 11/09/2020

Radio-Canada.ca - Création d'une nouvelle immunothérapie contre le cancer - 11/09/2020

MSN.com - L'immunothérapie bientôt plus efficace contre le cancer? - 12/09/2020

MLActu.fr - Cancer : une nouvelle immunothérapie permet de faire reculer la maladie chez la souris - 12/09/2020

DailyScience.be - Nouveau progrès à l’Institut de Duve en immunothérapie du cancer - 14/09/2020

DailyScience.be - Institut de Duve neemt nieuwe horde in immunotherapie tegen kanker - 14/09/2020

ArtsenKrant.com - Tregs in de schijnwerpers - 27/12/2020

Cordis.europa.eu - Entfesselung der natürlichen Körperabwehr gegen Krebs - 8/10/2021

Cordis.europa.eu - Desbloquear las defensas naturales del organismo contra el cáncer - 8/10/2021

Cope.es - Desarrollan una nueva inmunoterapia para vencer al cáncer - 11/09/2020

TweetSalud.com - Nueva inmunoterapia para vencer al cáncer - 15/09/2020

ElMira.es - El nuevo paso de la ciencia en la lucha contra el cáncer - 22/09/2020

NacioDigital.cat - Desenvolupen una nova immunoteràpia per vèncer el càncer - 22/09/2020

PatientWorthy.com - La Prueba de Células Inmunosupresoras Conduce a la Regresión Tumoral - 1/10/2020

Cordis.europa.eu - Sbloccare le difese naturali del corpo contro il cancro - 8/10/2021

NotizieScientifiche.it - Cancro, nuova immunoterapia fa regredire malattia nei topi​ - 11/09/2020

Fanpage.it - Nuova speranza nella lotta al cancro da un’innovativa applicazione terapeutica dell’immunoterapia - 12/09/2020

TuttoConoscenza.com - Immunoterapia contro il cancro: nuove scoperte - 19/09/2020

Cordis.europa.eu - Odblokowywanie naturalnej odpowiedzi przeciwnowotworowej organizmu - 8/10/2021

Bioon.com - Nat Commun：开发出一种对抗癌症的新型免疫疗法 - 12/09/2020

Daneshkadeha.com - ایمنوتراپی جدید برای غلبه بر سرطان - 2/10/2020

Also on EurekAlert.org, ScienceDaily.com, Brinkwire.com, BrightSurf.com, Knowledia.com, NewsColony.com, NewZealandOnlineNews.co.nz, LaMeuse.be, VivreIci.be, InfoSalus.com, ElIndependiente.com, ElPais.cr, and CantabriaLiberal.com

Funding

This work was supported by grants from the Fondation contre le Cancer, from the European Research Council (ERC), from the Actions de Recherche Concertées, from the FNRS and from the Région Wallonne.