Multifunctional Nanocomposites Modulating the Tumor Microenvironment for Enhanced Cancer Immunotherapy

Overview

Journal Bioact Mater

Specialty Biomedical Engineering

Date 2023 Sep 13

PMID 37701452

Authors

Prashant Sharma

Mario Otto

Affiliations

Soon will be listed here.

Abstract

Cancer immunotherapy has gained momentum for treating malignant tumors over the past decade. Checkpoint blockade and chimeric antigen receptor cell therapy (CAR-T) have shown considerable potency against liquid and solid cancers. However, the tumor microenvironment (TME) is highly immunosuppressive and hampers the effect of currently available cancer immunotherapies on overall treatment outcomes. Advancements in the design and engineering of nanomaterials have opened new avenues to modulate the TME. Progress in the current nanocomposite technology can overcome immunosuppression and trigger robust immunotherapeutic responses by integrating synergistic functions of different molecules. We will review recent advancements in nanomedical applications and discuss specifically designed nanocomposites modulating the TME for cancer immunotherapy. In addition, we provide information on the current landscape of clinical-stage nanocomposites for cancer immunotherapy.

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References

Dudek A, Martin S, Garg A, Agostinis P . Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity. Front Immunol. 2013; 4:438. PMC: 3858649. DOI: 10.3389/fimmu.2013.00438. View

Ojalvo L, Whittaker C, Condeelis J, Pollard J . Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors. J Immunol. 2009; 184(2):702-12. PMC: 3226722. DOI: 10.4049/jimmunol.0902360. View

Wang J, Wang Z, Li G . MicroRNA-125 in immunity and cancer. Cancer Lett. 2019; 454:134-145. DOI: 10.1016/j.canlet.2019.04.015. View

Sim G, Radvanyi L . The IL-2 cytokine family in cancer immunotherapy. Cytokine Growth Factor Rev. 2014; 25(4):377-90. DOI: 10.1016/j.cytogfr.2014.07.018. View

Chen Q, Wang C, Zhang X, Chen G, Hu Q, Li H . In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat Nanotechnol. 2018; 14(1):89-97. DOI: 10.1038/s41565-018-0319-4. View

Eruslanov E, Bhojnagarwala P, Quatromoni J, Stephen T, Ranganathan A, Deshpande C . Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014; 124(12):5466-80. PMC: 4348966. DOI: 10.1172/JCI77053. View

Wculek S, Cueto F, Mujal A, Melero I, Krummel M, Sancho D . Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2019; 20(1):7-24. DOI: 10.1038/s41577-019-0210-z. View

Denkert C, Liedtke C, Tutt A, von Minckwitz G . Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet. 2016; 389(10087):2430-2442. DOI: 10.1016/S0140-6736(16)32454-0. View

Dorand R, Nthale J, Myers J, Barkauskas D, Avril S, Chirieleison S . Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity. Science. 2016; 353(6297):399-403. PMC: 5051664. DOI: 10.1126/science.aae0477. View

10.

Rossetti R, Brand H, Lima S, Furtado I, Silveira R, Fantacini D . Combination of genetically engineered T cells and immune checkpoint blockade for the treatment of cancer. Immunother Adv. 2022; 2(1):ltac005. PMC: 9327125. DOI: 10.1093/immadv/ltac005. View

11.

Luo H, Lu L, Yang F, Wang L, Yang X, Luo Q . Nasopharyngeal cancer-specific therapy based on fusion peptide-functionalized lipid nanoparticles. ACS Nano. 2014; 8(5):4334-47. DOI: 10.1021/nn405989n. View

12.

Cook A, Lesterhuis W, Nowak A, Lake R . Chemotherapy and immunotherapy: mapping the road ahead. Curr Opin Immunol. 2016; 39:23-9. DOI: 10.1016/j.coi.2015.12.003. View

13.

Minchinton A, Tannock I . Drug penetration in solid tumours. Nat Rev Cancer. 2006; 6(8):583-92. DOI: 10.1038/nrc1893. View

14.

Schouppe E, De Baetselier P, Van Ginderachter J, Sarukhan A . Instruction of myeloid cells by the tumor microenvironment: Open questions on the dynamics and plasticity of different tumor-associated myeloid cell populations. Oncoimmunology. 2012; 1(7):1135-1145. PMC: 3494626. DOI: 10.4161/onci.21566. View

15.

Borden E . Interferons α and β in cancer: therapeutic opportunities from new insights. Nat Rev Drug Discov. 2019; 18(3):219-234. DOI: 10.1038/s41573-018-0011-2. View

16.

Yu P, Steel J, Zhang M, Morris J, Waldmann T . Simultaneous blockade of multiple immune system inhibitory checkpoints enhances antitumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model. Clin Cancer Res. 2010; 16(24):6019-28. PMC: 3005104. DOI: 10.1158/1078-0432.CCR-10-1966. View

17.

Arcucci A, Ruocco M, Granato G, Sacco A, Montagnani S . Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts. Biomed Res Int. 2016; 2016:4502846. PMC: 4993917. DOI: 10.1155/2016/4502846. View

18.

Lim M, Xia Y, Bettegowda C, Weller M . Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol. 2018; 15(7):422-442. DOI: 10.1038/s41571-018-0003-5. View

19.

Cousin S, Italiano A . Molecular Pathways: Immune Checkpoint Antibodies and their Toxicities. Clin Cancer Res. 2016; 22(18):4550-5. DOI: 10.1158/1078-0432.CCR-15-2569. View

20.

Yoon H, Selvan S, Yang Y, Kim M, Yi D, Kwon I . Engineering nanoparticle strategies for effective cancer immunotherapy. Biomaterials. 2018; 178:597-607. DOI: 10.1016/j.biomaterials.2018.03.036. View