Image-guided intratumoral immunotherapy: Developing a clinically practical technology

Som, Avik; Rosenboom, Jan‐Georg; Chandler, Alana; Sheth, Rahul A.; Wehrenberg-Klee, Eric

doi:10.1016/j.addr.2022.114505

Cited by 27 publications

(21 citation statements)

References 148 publications

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“…This is followed by an initiation phase where these DCs will activate T cells, which are allowed to activate when anti-CTLA-4 antibodies block T cells and dendritic cell suppressor signals. Finally, PD-1/PD-L1 antibodies will inhibit inhibitory signals from tumor cells, blocking the immune escape of tumor cells and exposing them to cytotoxic T-cell attacks ( 46 ).…”

Section: Application Of Intratumoral Immunotherapymentioning

confidence: 99%

“…Biocompatible polymers are ideal delivery pathways for immunotherapeutic drugs. Suitable delivery vehicles can be constructed for intra-tumor immunoadjuvants, including particle suspensions, polymer-drug couplings, and amphiphilic block polymers that self-assemble into nanoparticles ( 46 ). Early injectable formulations were mainly based on degradable and non-degradable particulate suspensions.…”

Section: Intratumoral Ablative Agents and Immunotherapy Drugsmentioning

confidence: 99%

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Chemo-immunoablation of solid tumors: A new concept in tumor ablation

2023

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Chemical ablation was designed to inject chemical agents directly into solid tumors to kill cells and is currently only used clinically for the palliative treatment of tumors. The application and combination of different drugs, from anhydrous ethanol, and glacial acetic acid to epi-amycin, have been clinically tested for a long time. The effectiveness is unsatisfactory due to chemical agents’ poor diffusion and concentration. Immunotherapy is considered a prospective oncologic therapeutic. Still, the clinical applications were limited by the low response rate of patients to immune drugs and the immune-related adverse effects caused by high doses. The advent of intratumoral immunotherapy has well addressed these issues. However, the efficacy of intratumoral immunotherapy alone is uncertain, as suggested by the results of preclinical and clinical studies. In this study, we will focus on the research of immunosuppressive tumor microenvironment with chemoablation and intratumoral immunotherapy, the synergistic effect between chemotherapeutic drugs and immunotherapy. We propose a new concept of intratumoral chemo-immunoablation. The concept opens a new perspective for tumor treatment from direct killing of tumor cells while, enhancing systemic anti-tumor immune response, and significantly reducing adverse effects of drugs.

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Section: Application Of Intratumoral Immunotherapymentioning

confidence: 99%

Section: Intratumoral Ablative Agents and Immunotherapy Drugsmentioning

confidence: 99%

Chemo-immunoablation of solid tumors: A new concept in tumor ablation

2023

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“…The molecular weight can also control the hydrophilicity of polymers. In general, a lower molecular weight is associated with higher hydrophilicity, thus leading to faster drug release. , In addition, hydrophilicity is a key factor for drug encapsulation and the aqueous solubility of biomaterial platforms. Injectable hydrogels often utilize hydrophobic–hydrophilic–hydrophobic (ABA-triblock) copolymers for the delivery of hydrophobic drugs.…”

Section: Perspectivesmentioning

confidence: 99%

Biomaterial-Based Sustained-Release Drug Formulations for Localized Cancer Immunotherapy

Mujahid,

Rana,

Suliman

et al. 2023

ACS Appl. Bio Mater.

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Cancer immunotherapy has revolutionized clinical cancer treatments by taking advantage of the immune system to selectively and effectively target and kill cancer cells. However, clinical cancer immunotherapy treatments often have limited efficacy and/or present severe adverse effects associated primarily with their systemic administration. Localized immunotherapy has emerged to overcome these limitations by directly targeting accessible tumors via local administration, reducing potential systemic drug distribution that hampers drug efficacy and safety. Sustained-release formulations can prolong drug activity at target sites, which maximizes the benefits of localized immunotherapy to increase the therapeutic window using smaller dosages than those used for systemic injection, avoiding complications of frequent dosing. The performance of sustained-release formulations for localized cancer immunotherapy has been validated preclinically using various implantable and injectable scaffold platforms. This review introduces the sustained-release formulations developed for localized cancer immunotherapy and highlights their biomaterial-based platforms for representative classes, including inorganic scaffolds, natural hydrogels, synthetic hydrogels, and microneedle patches. The design rationale and other considerations are summarized for further development of biomaterials for the construction of optimal sustained-release formulations.

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“…However, most will not be translated clinically due to safety concerns, funding scarcity, and lack of demonstrated efficacy, 18 in addition to failure to address clinicians' needs. 19 The goal of the present work was to develop a novel hydrogel that met the following criteria, which we believe are necessary for clinical translation. A clinically useful hydrogel must be (1) shear-thinning and self-healing, (2) biocompatible, (3) biodegradable, (4) clinically imageable, and (5) capable of sustained local release of biologically active immunotherapeutics.…”

Section: ■ Introductionmentioning

confidence: 99%

Characterization of an Injectable Chitosan Hydrogel for the Tunable, Localized Delivery of Immunotherapeutics

Mantooth,

Hancock,

Thompson

et al. 2024

ACS Biomater. Sci. Eng.

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Localized delivery of immunotherapeutics within a tumor has the potential to reduce systemic toxicities and improve treatment outcomes in cancer patients. Unfortunately, local retention of therapeutics following intratumoral injection is problematic and is insufficiently considered. Dense tumor architectures and high interstitial pressures rapidly exclude injections of saline and other low-viscosity solutions. Hydrogel-based delivery systems, on the other hand, can resist shear forces that cause tumor leakage and thus stand to improve the local retention of coformulated therapeutics. The goal of the present work was to construct a novel, injectable hydrogel that could be tuned for localized immunotherapy delivery. A chitosan-based hydrogel, called XCSgel, was developed and subsequently characterized. Nuclear magnetic resonance studies were performed to describe the chemical properties of the new entity, while cryo-scanning electron microscopy allowed for visualization of the hydrogel's cross-linked network. Rheology experiments demonstrated that XCSgel was shear-thinning and self-healing. Biocompatibility studies, both in vitro and in vivo, showed that XCSgel was nontoxic and induced transient mild-to-moderate inflammation. Release studies revealed that coformulated immunotherapeutics were released over days to weeks in a charge-dependent manner. Overall, XCSgel displayed several clinically important features, including injectability, biocompatibility, and imageability. Furthermore, the properties of XCSgel could also be controlled to tune the release of coformulated immunotherapeutics.

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Image-guided intratumoral immunotherapy: Developing a clinically practical technology

Cited by 27 publications

References 148 publications

Chemo-immunoablation of solid tumors: A new concept in tumor ablation

Chemo-immunoablation of solid tumors: A new concept in tumor ablation

Biomaterial-Based Sustained-Release Drug Formulations for Localized Cancer Immunotherapy

Characterization of an Injectable Chitosan Hydrogel for the Tunable, Localized Delivery of Immunotherapeutics

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