ArticleJournal for immunotherapy of cancer2021
Influence of injection technique, drug formulation and tumor microenvironment on intratumoral immunotherapy delivery and efficacy.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 124 citations in OpenAlex.
- Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept treatment strategy.Frontiers in immunology · 2025Trial
- Recent advances in interstitial fluid dynamics for diagnostic, targeted drug delivery and precision medicine applications.Drug delivery and translational research · 2026Review
- Fracking in Tumors: A Key Drug Transport Mechanism.Annals of biomedical engineering · 2026Article
- The closer, the better: intratumoral delivery of a thermoresponsive gemcitabine-loaded hydrogel in preclinical PDAC models.Drug delivery and translational research · 2026Article
- Radiopaque microsphere-hydrogel composite for extended-release intratumoral immunotherapy in a large animal model.Drug delivery and translational research · 2026Article
- Evaluation of multi-port needles for enhanced intramuscular drug delivery via experimental and CFD models.Journal of drug delivery science and technology · 2026Article
- PDIA6 promotes the cell proliferation of ESCC by enhancing the disulfide bond formation in TRAF4.Cellular & molecular biology letters · 2026Article
- Cancer cell-dependent increase in senescence-like populations following exosome treatment: The role of extracellular matrix and cellular glycocalyx.World journal of stem cells · 2026Article
- Advancements in intratumoral therapies for liver tumors.Frontiers in oncology · 2026Review
- Harnessing SARS-CoV-2 immunity to promote antitumor responses through intratumoral vaccination and adoptive transfer.Frontiers in immunology · 2026Article
- Chitosan-Glycerol Injectable Hydrogel for Intratumoral Delivery of Macromolecules.Gels (Basel, Switzerland) · 2025Article
- Review
- Efficient chemo-immunotherapy leveraging minimalist electrostatic complex nanoparticle as "in situ" vaccine integrated tumor ICD and immunoagonist.Journal of advanced research · 2025Article
- Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors.Journal for immunotherapy of cancer · 2025Article
- Intratumoral immunotherapy prior to cancer surgery, a promising therapeutic approach.Frontiers in immunology · 2025Review
- Mapping drug distribution using CT imaging following direct tissue injection in ex vivo liver: informing clinical implementation.CVIR oncology · 2025Article
- Testing Oncolytic Myxoma Virus in Immunocompetent Mouse Model for Cancer Therapy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Backflow reduction in local injection therapy with gelatin formulations.Drug delivery · 2024Article
- Virus nanotechnology for intratumoural immunotherapy.Nature reviews bioengineering · 2024Article
- Alternative Strategies for Delivering Immunotherapeutics Targeting the PD-1/PD-L1 Immune Checkpoint in Cancer.Pharmaceutics · 2024Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIntratumoral delivery of immunotherapeutics represents a compelling solution to directly address local barriers to tumor immunity. However, we have previously shown that off-target delivery is a substantial problem during intratumoral injections; this can lead to diminished drug efficacy and systemic toxicities. We have identified three variables that influence intratumoral drug delivery: injection technique, drug formulation and tumor microenvironment. The purpose of this study was to characterize the impact of modifications in each variable on intratumoral drug delivery and immunotherapy efficacy.
methodsIntratumoral injections were performed in a hybrid image-guided intervention suite with ultrasound, fluoroscopy and CT scanning capabilities in both rat and mouse syngeneic tumor models. Intratumoral drug distribution was quantified by CT volumetric imaging. The influence of varying needle design and hydrogel-based drug delivery on the immune response to a stimulator of interferon genes (STING) agonist was evaluated using flow cytometry and single cell RNA sequencing. We also evaluated the influence of tumor stiffness on drug injection distribution.
resultsVariations in needle design, specifically with the use of a multiside hole needle, led to approximately threefold improvements in intratumoral drug deposition relative to conventional end-hole needles. Likewise, delivery of a STING agonist through a multiside hole needle led to significantly increased expression of type I interferon-associated genes and 'inflammatory' dendritic cell gene signatures relative to end-hole STING agonist delivery. A multidomain peptide-based hydrogel embedded with a STING agonist led to substantial improvements in intratumoral deposition; however, the hydrogel was noted to generate a strong immune response against itself within the target tumor. Evaluation of tumor stroma on intratumoral drug delivery revealed that there was a greater than twofold improvement in intratumoral distribution in soft tumors (B16 melanoma) compared with firm tumors (MC38 colorectal).
conclusionsInjection technique, drug formulation and tumor stiffness play key roles in the accurate delivery of intratumoral immunotherapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.