Novel Delivery Systems for Checkpoint Inhibitors

Lamichhane, Purushottam; Deshmukh, Rahul; Brown, Julie; Jakubski, Silvia; Parajuli, Priyanka; Nolan, Todd A.; Raja, Dewan; Badawy, Mary; Yoon, Thomas; Zmiyiwsky, Mark; Lamichhane, Narottam

doi:10.3390/medicines6030074

Cited by 22 publications

(21 citation statements)

References 163 publications

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“…115 Various delivery systems for immune checkpoint modulators, including platelet, viral and bacterial vectors are also under active investigation. 116 Caplacizumab, a nanobody targeting von Willebrand factor, recently received the first ever FDA approval for a nanobodydirected therapy. 117 KN035, an anti-PD-L1 IgV-type nanobody has been shown to bind chiefly through a 21 amino acid segment that includes the Ile54, Tyr56 and Arg113 residues which participate in the PD-1 interaction.…”

Section: Alternative Mechanisms Of Immune Modulation For T Lymphocytementioning

confidence: 99%

T lymphocyte-targeted immune checkpoint modulation in glioma

Kelly

Giles

Gilbert

2020

J Immunother Cancer

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Immunomodulatory therapies targeting inhibitory checkpoint molecules have revolutionized the treatment of solid tumor malignancies. Concerns about whether systemic administration of an immune checkpoint inhibitor could impact primary brain tumors were answered with the observation of definitive responses in pediatric patients harboring hypermutated gliomas. Although initial clinical results in patients with glioblastoma (GBM) were disappointing, recently published results have demonstrated a potential survival benefit in patients with recurrent GBM treated with neoadjuvant programmed cell death protein 1 blockade. While these findings necessitate verification in subsequent studies, they support the possibility of achieving clinical meaningful immune responses in malignant primary brain tumors including GBM, a disease in dire need of additional therapeutic options. There are several challenges involved in treating glioma with immune checkpoint modulators including the immunosuppressive nature of GBM itself with high inhibitory checkpoint expression, the immunoselective blood brain barrier impairing the ability for peripheral lymphocytes to traffic to the tumor microenvironment and the high prevalence of corticosteroid use which suppress lymphocyte activation. However, by simultaneously targeting multiple costimulatory and inhibitory pathways, it may be possible to achieve an effective antitumoral immune response. To this end, there are now several novel agents targeting more recently uncovered “second generation” checkpoint molecules. Given the multiplicity of drugs being considered for combination regimens, an increased understanding of the mechanisms of action and resistance combined with more robust preclinical and early clinical testing will be needed to be able to adequately test these agents. This review summarizes our current understanding of T lymphocyte-modulating checkpoint molecules as it pertains to glioma with the hope for a renewed focus on the most promising therapeutic strategies.

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Section: Alternative Mechanisms Of Immune Modulation For T Lymphocytementioning

confidence: 99%

T lymphocyte-targeted immune checkpoint modulation in glioma

Kelly

Giles

Gilbert

2020

J Immunother Cancer

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“…[ 58 ] So far, considerable efforts have been dedicated to enhance precise delivery of immunomodulators, increase the uptake of therapeutic cancer vaccines, and improve engineering efficiency of T cells. [ 59 ] Introducing the micro‐or nano‐sized robots into immunotherapy broadens the avenue. Current research works proved that MNMs can work hands in hands with the immune system in the fight against cancer, achieving efficient activation of T cells, and delivery of immune checkpoint inhibitors/therapeutic cancer vaccines.…”

Section: Applications In the Immune Systemmentioning

confidence: 99%

“…Tumor‐targeting delivery vehicles such as liposomes, nanoparticles, dendrimers, injectable hydrogels, and viral vectors rely on the enhanced permeation and retention effect in diseased tissues. [ 59b ] Yet such targeting strategies are limited by off‐target toxicity. Moreover, common drug delivery systems lack sufficient energy to overcome cells, tissues, and other biological obstacles.…”

Section: Applications In the Immune Systemmentioning

confidence: 99%

Interactions between Biomedical Micro‐/Nano‐Motors and the Immune Molecules, Immune Cells, and the Immune System: Challenges and Opportunities

Wang

et al. 2021

Adv Healthcare Materials

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Mobile micro‐ and nano‐motors (MNMs) emerge as revolutionary platforms for biomedical applications, including drug delivery, biosensing, non‐invasive surgery, and cancer therapy. While for applications in biomedical fields and practical clinical translation, the interactions of these untethered tiny machines with the immune system is an essential issue to be considered. This review highlights the recent approaches of surpassing immune barriers to prevent foreign motors from triggering immune responses. In addition to trials focusing on the function preservation of MNMs, examples of versatile MNMs working with the immune components (immune molecules, immune cells and the whole system) to achieve cancer immunotherapy, immunoassay, and detoxification are outlined. The immune interference part provides researchers an idea about what is the limit presented by the immune components. The coworking part suggests ways to bypass or even utilize the limit. With interdisciplinary cooperation of nanoengineering, materials science, and immunology field, the rationally designed functional MNMs are expected to provide novel opportunities for the biomedical field.

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“…Despite research continuing to elucidate the efficacies of checkpoint inhibitors in treatments of cancers, the scope limitations are not entirely clear. Toxicities continue to be a major issue with the systematic use of checkpoint inhibitors [ 65 ]. Furthermore, while combination checkpoint blockade regimens have yielded better response rates and overall survivals, the tradeoff includes a significant increase in severe toxicities.…”

Section: Types Of Immunotherapy: Their Combinations and Limitationmentioning

confidence: 99%

“…Through any treatment plan, the objectives are to improve the lifespan of patients while having minimal side effects during the process. Targeted delivery of checkpoint inhibitors may alleviate these systematic effects while maintaining or even improving the efficacies [ 65 ].…”

Section: Types Of Immunotherapy: Their Combinations and Limitationmentioning

confidence: 99%

Immunotherapies and Combination Strategies for Immuno-Oncology

Barbari

Fontaine

Parajuli

et al. 2020

IJMS

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The advent of novel immunotherapies in the treatment of cancers has dramatically changed the landscape of the oncology field. Recent developments in checkpoint inhibition therapies, tumor-infiltrating lymphocyte therapies, chimeric antigen receptor T cell therapies, and cancer vaccines have shown immense promise for significant advancements in cancer treatments. Immunotherapies act on distinct steps of immune response to augment the body’s natural ability to recognize, target, and destroy cancerous cells. Combination treatments with immunotherapies and other modalities intend to activate immune response, decrease immunosuppression, and target signaling and resistance pathways to offer a more durable, long-lasting treatment compared to traditional therapies and immunotherapies as monotherapies for cancers. This review aims to briefly describe the rationale, mechanisms of action, and clinical efficacy of common immunotherapies and highlight promising combination strategies currently approved or under clinical development. Additionally, we will discuss the benefits and limitations of these immunotherapy approaches as monotherapies as well as in combination with other treatments.

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Novel Delivery Systems for Checkpoint Inhibitors

Cited by 22 publications

References 163 publications

T lymphocyte-targeted immune checkpoint modulation in glioma

T lymphocyte-targeted immune checkpoint modulation in glioma

Interactions between Biomedical Micro‐/Nano‐Motors and the Immune Molecules, Immune Cells, and the Immune System: Challenges and Opportunities

Immunotherapies and Combination Strategies for Immuno-Oncology

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