Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges

Martin, John D.; Cabral, Horacio; Stylianopoulos, Triantafyllos; Jain, Rakesh K.

doi:10.1038/s41571-019-0308-z

Cited by 469 publications

(398 citation statements)

References 203 publications

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“…In addition, a clinical study found that anti-CTLA-4 immunotherapy does not deplete regulatory T cells (64). Tumor types might have a significantly different immunologic background, and thus the identification of common predictive markers based on molecular information is extremely challenging (7). On the other hand, tumor perfusion can be measured in patients and should be tested as a biomarker in prospective trials.…”

Section: Discussionmentioning

confidence: 99%

“…The absence of a therapeutic benefit in patients has been attributed to a variety of factors, including the abnormal tumor microenvironment (TME), characterized by dysfunctional blood vessels that hinder the delivery of immunotherapeutic agents and cause immunosuppression (1,6,7). Indeed, a spatiotemporal lack of sufficient tumor blood perfusion can result in hypoxia, low pH, and inadequate delivery of medicines, which in turn compromises the efficacy of cancer therapies, including immunotherapy (1,8,9).…”

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confidence: 99%

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Combining microenvironment normalization strategies to improve cancer immunotherapy

Mpekris

Voutouri

Baish

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

198

143

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Advances in immunotherapy have revolutionized the treatment of multiple cancers. Unfortunately, tumors usually have impaired blood perfusion, which limits the delivery of therapeutics and cytotoxic immune cells to tumors and also results in hypoxia-a hallmark of the abnormal tumor microenvironment (TME)-that causes immunosuppression. We proposed that normalization of TME using antiangiogenic drugs and/or mechanotherapeutics can overcome these challenges. Recently, immunotherapy with checkpoint blockers was shown to effectively induce vascular normalization in some types of cancer. Although these therapeutic approaches have been used in combination in preclinical and clinical studies, their combined effects on TME are not fully understood. To identify strategies for improved immunotherapy, we have developed a mathematical framework that incorporates complex interactions among various types of cancer cells, immune cells, stroma, angiogenic molecules, and the vasculature. Model predictions were compared with the data from five previously reported experimental studies. We found that low doses of antiangiogenic treatment improve immunotherapy when the two treatments are administered sequentially, but that high doses are less efficacious because of excessive vessel pruning and hypoxia. Stroma normalization can further increase the efficacy of immunotherapy, and the benefit is additive when combined with vascular normalization. We conclude that vessel functionality dictates the efficacy of immunotherapy, and thus increased tumor perfusion should be investigated as a predictive biomarker of response to immunotherapy.immunotherapy | vascular function | normalization | anti-angiogenic therapy | mechanotherapeutics

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Combining microenvironment normalization strategies to improve cancer immunotherapy

Mpekris

Voutouri

Baish

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

198

143

View full text Add to dashboard Cite

show abstract

“…[159,160] While these recent advances in local drug delivery technologies are seemingly poised to offer unparalleled opportunities to transform cancer treatment approaches, regulatory hurdles need to be addressed prior to clinical translation. Cumulative efforts in controlled drug delivery research [161] along with advances in therapeutic oncology, [162][163][164] have better equipped us to devise more effective local delivery systems, confront translational hurdles, and provide safer solutions for cancer treatment.…”

Section: Resultsmentioning

confidence: 99%

Emerging Technologies for Local Cancer Treatment

Chua

Demaria

et al. 2020

Advanced Therapeutics

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The fundamental limitations of systemic therapeutic administration have prompted the development of local drug delivery platforms as a solution to increase effectiveness and reduce side effects. By confining therapeutics to the site of disease, local delivery technologies can enhance therapeutic index. This review highlights recent advances and opportunities in local drug delivery strategies for cancer treatment in addition to challenges that need to be addressed to facilitate clinical translation. The benefits of local cancer treatment combined with technological advancements and increased understanding of the tumor microenvironment, present a prime breakthrough opportunity for safer and more effective therapies.

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“…TME, which is characterized by hypoxia, low pH, and high interstitial fluid pressure, facilitates tumor aggression and hinders the efficacy of antitumor therapies including immu notherapy on account of the limited distribution and accumu lation of either drugs or immune cells. [59,60] Therefore, TME regulation began to get on the stage as an attractive strategy to improve the effectiveness of immunotherapy. [61] With the help of RBC membranecoated nanoparticles, sustained and pro longed delivery of TMEregulating agents is possible.…”

Section: Tme Regulationmentioning

confidence: 99%

Improving Cancer Immunotherapy by Cell Membrane‐Camouflaged Nanoparticles

Zeng

2020

Adv Funct Materials

135

103

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Cancer immunotherapy has received tremendous attention in the past decade owing to its clinical successes with the use of immune-checkpoint inhibition and chimeric antigen receptor T cell therapy. However, only a small proportion of the patients have benefited from these immunotherapeutic drugs, which has raised concerns about the low response rate and immune-related adverse events. Nanomedicines have served as a paradigm for preferential tumor accumulation but still confront issues such as poor circulation and insufficient tumor accumulation. By virtue of coating nanoparticles with cell membranes from diverse cell sources, active proteins on cell membranes can impart a variety of desired functionalities or supplementary therapeutic effects to nanoparticles, providing ways for enhanced cancer immunotherapy. In this review, the recent advances of cell membrane camouflaged nanoparticles applied to the improved immunotherapy are discussed on the basis of different sources of cell membranes and corresponding working mechanisms. These biomimetic nanoparticles can potentially deliver therapeutic agents to the designated sites and actively engage in particular stages of the cancer immunity cycle, eliciting antitumor immunity with less off-target toxicities.

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Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges

Cited by 469 publications

References 203 publications

Combining microenvironment normalization strategies to improve cancer immunotherapy

Combining microenvironment normalization strategies to improve cancer immunotherapy

Emerging Technologies for Local Cancer Treatment

Improving Cancer Immunotherapy by Cell Membrane‐Camouflaged Nanoparticles

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