Management of lymph node metastasis via local chemotherapy can prevent distant metastasis and improve survival in mice

Kim, Heegon; Han, Hyeonjeong; Jeong, Minwoo; Han, Junhee; Park, Ji-Ho

doi:10.1016/j.jconrel.2020.10.016

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Local administration via either the PT or IT route has been previously exploited for in situ vaccination ( 3 , 20 ). Following local administration, agents with a diameter of 10–100 nm efficiently travel within the tissue and drain into the local lymphatic system ( 20 , 25 – 27 ). In addition, proper surface engineering with soluble polymers, such as PEG, is required to facilitate their clearance from the injection site and efficient transport through the interstitial matrix ( 27 , 28 ).…”

Section: Resultsmentioning

confidence: 99%

“…Following local administration, agents with a diameter of 10–100 nm efficiently travel within the tissue and drain into the local lymphatic system ( 20 , 25 – 27 ). In addition, proper surface engineering with soluble polymers, such as PEG, is required to facilitate their clearance from the injection site and efficient transport through the interstitial matrix ( 27 , 28 ). Thus, the feasibility of local administration of PEGylated micelle formulations to tumors and TDLNs was assessed.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Coimmunomodulation of tumor and tumor-draining lymph nodes during in situ vaccination promotes antitumor immunity

Jeong¹,

Kim²,

Yoon³

et al. 2022

JCI Insight

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In situ vaccination has demonstrated the feasibility of priming local immunity for systemic antitumor responses. Although direct intratumoral (IT) delivery of adjuvant is the mainstay, tumor-draining lymph nodes (TDLNs) also play essential roles in antitumor immunity. We report that directing an adjuvant to both tumors and TDLNs during in situ vaccination can induce robust antitumor responses. Conventional IT dosing leads to tumor-limited delivery of agents; however, delivery to both tumors and TDLNs can be ensured through a micellar formation. The peritumoral delivery of micellar MEDI9197 (mcMEDI), a toll-like receptor 7/8 agonist, induced significantly stronger innate and adaptive immune responses than those on conventional dosing. Optimal dosing was crucial because excessive or insufficient accumulation of the adjuvant in the TDLNs compromised therapeutic efficacy. The combination of local mcMEDI therapy significantly improved the efficacy of systemic anti–programmed death receptor 1 therapy. These data suggest that rerouting adjuvants to tumors and TDLNs can augment the therapeutic efficacy of in situ vaccination.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Coimmunomodulation of tumor and tumor-draining lymph nodes during in situ vaccination promotes antitumor immunity

Jeong¹,

Kim²,

Yoon³

et al. 2022

JCI Insight

Self Cite

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“…Once the tumor has metastasized to distant organs, MBC is largely untreatable due to limited treatment options, and survival after 5 years is only about 20%, however, the overall 5-year survival rate of patients with BCLM is even only 16.8%. The data demonstrates that 60%-70% of patients who die from BCLM (Schlappack et al, 1988;Smid et al, 2008;Nguyen et al, 2009;Eckhardt et al, 2012;Lee et al, 2019;Kim et al, 2021). Despite ongoing efforts by researchers to treat breast cancer, overcoming advanced tumor metastasis is still a great challenge in cancer therapy, which often leads to treatment failure.…”

Section: Introductionmentioning

confidence: 99%

Nanotechnology for the theranostic opportunity of breast cancer lung metastasis: recent advancements and future challenges

Miao,

Kang,

Zhang

2024

Front. Bioeng. Biotechnol.

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Lung metastasis of breast cancer is rapidly becoming a thorny problem in the treatment of patients with breast cancer and an obstacle to long-term survival. The main challenges of treatment are the absence of therapeutic targets and drug resistance, which promotes the development of nanotechnology in the diagnosis and treatment process. Taking advantage of the controllability and targeting of nanotechnology, drug-targeted delivery, controlled sustained release, multi-drug combination, improved drug efficacy, and reduced side effects can be realized in the process of the diagnosis and treatment of metastatic breast cancer (MBC). Several nanotechnology-based theranostic strategies have been investigated in breast cancer lung metastases (BCLM): targeted drug delivery, imaging analysis, immunotherapy, gene therapy, and multi-modality combined therapy, and some clinical applications are in the research phase. In this review, we present current nanotechnology-based diagnosis and treatment approaches for patients of incurable breast cancer with lung metastases, and we hope to be able to summarize more effective and promising nano-drug diagnosis and treatment systems that aim to improve the survival of patients with advanced MBC. We describe nanoplatform-based experimental studies and clinical trials targeting the tumor and the tumor microenvironment (TME) for BCLM to obtain more targeted treatment and in the future treatment steps for patients to provide a pioneering strategy.

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“…To reduce chemotherapy-related cytotoxicity, local delivery of chemotherapeutic drugs was proposed as a method to maximize local drug concentrations in the immediate tumor environment while also minimizing systemic exposure and nontarget organ toxicity (6,7). In models of lymph node metastasis, the antitumor efficacy of local chemotherapy for regional lymph node metastasis was reported to be better than that of systemic chemotherapy, and the treatment was deemed to be safe (8). The development of interventional therapy provides a new approach for the local delivery of chemotherapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

A Local and Low-Dose Chemotherapy/Autophagy-Enhancing Regimen Treatment Markedly Inhibited the Growth of Established Solid Tumors Through a Systemic Antitumor Immune Response

Yuan

et al. 2021

Front. Oncol.

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Chemotherapy is one of the main options for the treatment of a variety of malignant tumors. However, the severe side effects resulting from the killing of normal proliferating cells limit the application of cancer-targeting chemotherapeutic drugs. To improve the efficacy of classic systemic chemotherapy, the local delivery of high-dose chemotherapeutic drugs was developed as a method to enhance local drug concentrations and minimize systemic toxicity. Studies have demonstrated that chemotherapy is often accompanied by cancer-associated immunogenic cell death (ICD) and that autophagy is involved in the induction of ICD. To improve the efficacy of local cancer chemotherapy, we hypothesized that the local delivery of chemotherapeutic plus autophagy-enhancing agents would enhance the promotive effects of ICD on the antitumor immune response. Here, we report that a low-dose chemotherapy/autophagy enhancing regimen (CAER) not only resulted in the increased death of B16F10 and 4T1 tumor cells, but also induced higher levels of autophagy in vitro. Importantly, the local delivery of the CARE drugs significantly inhibited tumor growth in B16F10 and 4T1 tumor-bearing mice. Systemic antitumor T-cell immunity was observed in vivo, including neoantigen-specific T-cell responses. Furthermore, bioinformatic analysis of human breast cancer and melanoma tissues showed that autophagy-associated gene expression was upregulated in tumor samples. Increased autophagy and immune cell infiltration in tumor tissues were positively correlated with good prognosis of tumor patients. This work highlights a new approach to improve the effects of local chemotherapy and enhance systemic antitumor immunity.

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Management of lymph node metastasis via local chemotherapy can prevent distant metastasis and improve survival in mice

Cited by 7 publications

References 38 publications

Coimmunomodulation of tumor and tumor-draining lymph nodes during in situ vaccination promotes antitumor immunity

Coimmunomodulation of tumor and tumor-draining lymph nodes during in situ vaccination promotes antitumor immunity

Nanotechnology for the theranostic opportunity of breast cancer lung metastasis: recent advancements and future challenges

A Local and Low-Dose Chemotherapy/Autophagy-Enhancing Regimen Treatment Markedly Inhibited the Growth of Established Solid Tumors Through a Systemic Antitumor Immune Response

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