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Combinatorial activation of anti-tumour immunity using innovative multi-targeted nano-immunotherapeutics

English title Combinatorial activation of anti-tumour immunity using innovative multi-targeted nano-immunotherapeutics
Applicant Jandus Camilla
Number 183284
Funding scheme India
Research institution Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Immunology, Immunopathology
Start/End 01.05.2019 - 30.04.2023
Approved amount 349'464.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Experimental Cancer Research

Keywords (5)

nanotechnologies; immunotherapy; cancer; cold tumors; spatio-temporal targeted delivery

Lay Summary (French)

Lead
Activation de l'immunité anti-tumorale à l'aide de nouveaux nano-immunothérapies à cibles multiples
Lay summary
L'immunologie tumorale et l'immunothérapie ont récemment pris une place centrale dans la recherche sur le cancer. Il s'agit d'un traitement qui mobilise les cellules immunitaires de l'organisme pour traquer les cellules cancéreuses dans l'organisme et les tuer. L'immunothérapie est déjà utilisée dans la clinique, mais seule une proportion limitée de patients répond au traitement. Par conséquent, il est nécessaire d'accroître l'efficacité clinique chez un plus grand nombre de patients traités et de réduire au minimum la toxicité. Des interventions ciblant la modification du microenvironnement tumoral immunosuppressif seront essentielles pour augmenter et soutenir la phase effectrice des cellules immunitaires, pour favoriser la reconnaissance immunitaire et pour surmonter la suppression du système immunitaire. Les nanotechnologies représentent une approche novatrice prometteuse pour aider à l'optimisation de l'immunothérapie du cancer, en permettant l'administration ciblée, spatio-temporelle et combinatoire contrôlée d'agents d'immunothérapie puissants. Dans ce projet, nous envisageons d'intégrer l'expertise des équipes suisse et indienne en immunologie/immunothérapie du cancer et en nanotechnologies, respectivement, pour développer de puissantes nanoparticules pour cibler le système immunitaire  inné et adaptatif. Nous proposons d'exploiter différents types de nanoparticules pour développer une plateforme innovante de nanoparticules pour cibler les agents immunomodulateurs au site tumoral et dans les ganglions lymphatiques drainant, avec différentes cinétiques, dans un modèle préclinique du mélanome. Les résultats de ce projet devraient contribuer à l'optimisation rapide des immunothérapies actuelles afin d'améliorer les bienfaits cliniques chez les patients.
Direct link to Lay Summary Last update: 17.12.2018

Responsible applicant and co-applicants

Gesuchsteller/innen Ausland

Employees

Project partner

Collaboration

Group / person Country
Types of collaboration
Amrita Centre for Nanoscience and Molecular Medicine India (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel

Scientific events



Self-organised

Title Date Place
Mini Symposium 13.05.2022 Lausanne, Switzerland

Abstract

Despite remarkable recent achievements of immunotherapy strategies in cancer treatment, in particular by the use of immune checkpoint inhibitors (anti-CTLA4 and anti-PD-1 antibodies), clinical responses remain limited to subsets of patients. Hence, there is a need to increase clinical efficacy to higher proportions of treated patients, as well as to minimize toxicity. Disruption of immune regulatory circuits and local immune editing in the tumour microenvironment will be key to increase and sustain the immune cell effector phase, to favour immune recognition and overcome suppression of the immune system. Nanotechnologies represents a promising innovative approach to assist in the optimization of cancer immunotherapy, by enabling targeted, spatio-temporal, combinatorial controlled delivery of potent immunotherapy agents. In this project, we envisage to integrate the expertise of the Swiss and Indian teams in cancer immunology/immunotherapy and nanotechnologies, respectively, to develop potent nanoparticle-based integrated innate-adaptive immune system targeting therapies. In Aim 1, we propose to harness various types of nanoparticles to develop an innovative multicomponent-based nanoparticle platform to target immunomodulatory agents to the tumor site and its draining lymph nodes, with different kinetics, in a preclinical melanoma model. First, a V-type nanoparticle will form an innovative cancer vaccine incorporating synthetic peptides encoding for tumor antigens, in combination with potent immune adjuvants. The second hydrogel based nano-immunotherapy component will be loaded with pro-inflammatory cytokines, implanted near to the draining lymph node for a sustained cytokine release to promote potent effector anti-tumour immunity. The third nano-particle component will be packed with inhibitors of potent immunosuppressive molecules, and by its direct intratumoural injection it is expected to counteract in situ established immunosuppressive networks, that are inhibiting efficient anti-tumour responses. Overall, the spatio-temporal, combinatorial controlled delivery of the 3 components is expected to enhance and prolong the effector phase of anti-tumour immunity and feed forward an aggressive innate and adaptive immune response, that will be comprehensively assessed using state-of-the art in vivo and in vitro immunomonitoring technologies. Next, in Aim 2, we propose to exploit nano-immunotherapeutics to disrupt mechanisms underlying resistance to PD-1/PD-L1 blockade therapy, by converting so-called “cold” tumors, that lack T cell infiltration, into T cell rich, immunotherapy-sensitive “hot” ones. We will deliver nanoparticles directly intratumorally in “cold” tumor models, in combination with anti-PD1 treatment, to interfere in a sustained manner with mechanisms that have emerged as key mediators of resistance to immune checkpoints. By performing tumor growth studies and comprehensive immune monitoring we will identify the best strategy for the sensitization of “cold” tumor to immunotherapy. Overall, the joint Swiss-Indian team will develop novel and safer combinatorial nano-immunotherapeutic platforms to orchestrate integrated innate-adaptive cancer immunotherapy through ground-breaking, proof-of-concept studies. The results of this project are expected to assist in the rapid optimization of current immunotherapies for improved clinical benefit in patients.
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