Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma

Detappe, Alexandre; Reidy, Mairéad; Yu, Yingjie; Mathieu, Cécile; Nguyen, Hung V.-T.; Coroller, Thibaud P.; Lam, Fred C.; Jarolím, Petr; Harvey, P. K.; Protti, Andrea; Nguyen, Quang-Dé; Johnson, Jeremiah A.; Crémillieux, Yannick; Tillement, Olivier; Ghobrial, Irène M.; Ghoroghchian, P. Peter

doi:10.1039/c9nr06512a

Cited by 30 publications

(30 citation statements)

References 52 publications

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“…hence improving tumor cells accumulation. [71] However, because of their size, a high drug loading is difficult to achieve, orienting their use mostly for medical imaging applications. [33,34,71] At the opposite, the biodistribution and pharmacokinetics properties of large NPs (> 50 nm diameter) are dictated by the NP, resulting in a large accumulation in the liver and lymph nodes.…”

Section: Nanomedicine To Improve Immunotherapymentioning

confidence: 99%

“…[71] However, because of their size, a high drug loading is difficult to achieve, orienting their use mostly for medical imaging applications. [33,34,71] At the opposite, the biodistribution and pharmacokinetics properties of large NPs (> 50 nm diameter) are dictated by the NP, resulting in a large accumulation in the liver and lymph nodes. [72,73] This preferential accumulation into lymphatic vessels and lymph nodes is of interest to target immune cells for vaccination approach or for neoantigen recruitment after radiotherapy.…”

Section: Nanomedicine To Improve Immunotherapymentioning

confidence: 99%

“…It was demonstrated that the biodistribution and pharmacokinetics of ultrasmall NPs (< 5 nm diameter) are dictated by their ligand decoration, increasing their circulation time in the body and hence improving tumor cells accumulation. [ 71 ] However, because of their size, a high drug loading is difficult to achieve, orienting their use mostly for medical imaging applications. [ 33,34,71 ] At the opposite, the biodistribution and pharmacokinetics properties of large NPs (> 50 nm diameter) are dictated by the NP, resulting in a large accumulation in the liver and lymph nodes.…”

Section: Nanomedicine To Improve Immunotherapymentioning

confidence: 99%

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Leveraging Immunotherapy with Nanomedicine

Mittelheisser

Banerjee

Pivot

et al. 2020

Advanced Therapeutics

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Considerable progress has been made in the development and understanding of immunotherapy, notably with the emergence of novel chimeric antigen receptor T cells (CAR-T) which changed the perception of personalized therapy. However, cell-based immunotherapy not only lacks therapeutic efficiency in various solid cancers but also raises concerns related to important side effects. The convergence of immunotherapy and nanomedicine is timely as nanoparticles can now be easily conjugated to various antibodies and peptides enabling outstanding abilities to target specific cell populations in vivo. Here, the state of the art of immunonanotherapy that activates the immune system in vivo, by acting either as vaccines or as tumor microenvironment (TME) activators is described. Then, the development of ex vivo immune-cell surface labeling strategies is discussed to exploit immune cells as trojan horses and thereby improving the delivery of the therapeutics in the TME. Such a strategy is likely to considerably amplify the efficacy of immunotherapy.

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Section: Nanomedicine To Improve Immunotherapymentioning

confidence: 99%

Section: Nanomedicine To Improve Immunotherapymentioning

confidence: 99%

Section: Nanomedicine To Improve Immunotherapymentioning

confidence: 99%

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Leveraging Immunotherapy with Nanomedicine

Mittelheisser

Banerjee

Pivot

et al. 2020

Advanced Therapeutics

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“…[8] Recently, immunoPET radiotracers have been translated into the clinic due to the specificity of selected antibodies and the high sensitivity of PET imaging [9,10] . Preclinical studies involving immunoPET radiotracers (using antibodies or nanobodies) [11][12][13] and antibodyconjugated MRI tracers [14] have demonstrated the possibility of significantly improving longitudinal monitoring of MM. The development of novel immunoPET radiotracers is of keen interest due to their better signal-to-noise ratios (SNRs) over MRIbased methods and their ability to detect small clusters of cells, potentially enabling the identification of minimal residual disease (MRD), which is currently difficult with passive contrast agents for PET imaging.…”

Section: Introductionmentioning

confidence: 99%

“…Leveraging these promising results, we designed an innovative approach that targets the B-cell maturation antigen (BCMA) that is widely used as a therapeutic target in MM and that is highly expressed at all stages of the disease; notably, this approach differs from traditional methods that have instead targeted CD38, which is a transmembrane glycoprotein that is almost exclusively expressed on MM cells. [14] BCMA is a known target for chimeric antigen receptor (CAR) T-cell [15] and bispecific antibody therapy; [16] but, it has yet to be adopted for MM imaging. [17] While we previously successfully demonstrated that targeting BCMA for preclinical MRI-based imaging of MM is a relevant approach, [14] here, we hypothesized that the use of a immuno-nanoPET radiotracer would enable a decrease in the amount of mAb needed for injection in comparison to the amounts of im-munoPET radiotracer required to improve the sensitivity of PET imaging.…”

Section: Introductionmentioning

confidence: 99%

Anti‐BCMA Immuno‐NanoPET Radiotracers for Improved Detection of Multiple Myeloma

Thomas

Mathieu

Moreno-Gaona

et al. 2021

Adv Healthcare Materials

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Current clinical imaging modalities for the sensitive and specific detection of multiple myeloma (MM) rely on nonspecific imaging contrast agents based on gadolinium chelates for magnetic resonance imaging (MRI) or for 18 F-FDG-directed and combined positron emission tomography (PET) and computed tomography (CT) scans. These tracers are not, however, able to detect minute plasma cell populations in the tumor niche, leading to false negative results. Here, a novel PET-based anti-BCMA nanoplatform labeled with 64 Cu is developed to improve the monitoring of these cells in both the spine and femur and to compare its sensitivity and specificity to more conventional immunoPET ( 64 Cu labeled anti-BCMA antibody) and passively targeted PET radiotracers ( 64 CuCl 2 and 18 F-FDG). This proof-of-concept preclinical study confirmed that by conjugating up to four times more radioisotopes per antibody with the immuno-nanoPET platform, an improvement in the sensitivity and in the specificity of PET to detect tumor cells in an orthotopic model of MM is observed when compared to the traditional immunoPET approach. It is anticipated that when combined with tumor biopsy, this immuno-nanoPET platform may improve the management of patients with MM.

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Supramolecular Heterodimer Peptides Assembly for Nanoparticles Functionalization

Mathieu,

Ghosh,

Draussin

et al. 2024

Adv Healthcare Materials

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Nanoparticle (NP) surface functionalization with proteins, including monoclonal antibodies (mAbs), mAb fragments, and various peptides, has emerged as a promising strategy to enhance tumor targeting specificity and immune cell interaction. However, these methods often rely on complex chemistry and suffer from batch‐dependent outcomes, primarily due to limited control over the protein orientation and quantity on NP surfaces. To address these challenges, we present a novel approach based on the supramolecular assembly of two peptides to create a heterotetramer displaying VHHs on NP surfaces. This approach effectively targets both tumor‐associated antigens (TAAs) and immune cell‐associated antigens. In vitro experiments showcased its versatility, as we biofunctionalized various NP types, including liposomes, PLGA NPs, and ultrasmall silica‐based NPs, and evaluated the VHHs targeting of known TAAs (HER2 for breast cancer, CD38 for multiple myeloma) and an immune cell antigen (NKG2D for natural killer (NK) cells). In in vivo studies using a HER2+ breast cancer mouse model, our approach demonstrated enhanced tumor uptake, retention, and penetration compared to the behavior of nontargeted analogs, affirming its potential for diverse applications.This article is protected by copyright. All rights reserved

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Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma

Abstract: Monitoring malignant progression and disease recurrence post-therapy are central challenges to improving the outcomes of patients with multiple myeloma (MM).

Cited by 30 publications

References 52 publications

Leveraging Immunotherapy with Nanomedicine

Leveraging Immunotherapy with Nanomedicine

Anti‐BCMA Immuno‐NanoPET Radiotracers for Improved Detection of Multiple Myeloma

Supramolecular Heterodimer Peptides Assembly for Nanoparticles Functionalization

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