Intratumoral Immunotherapy and Tumor Ablation: A Local Approach with Broad Potential

Senders, Zachary J.; Martin, Robert C.G.

doi:10.3390/cancers14071754

Cited by 9 publications

(4 citation statements)

References 61 publications

(67 reference statements)

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“…Still, not all patients received benefits from ICIs therapy. However, intratumoral immunotherapy is now available in many preclinical and clinical trials and is gradually demonstrating its advantages ( 39 – 43 ). Although most immunotherapy is currently administered intravenously, the larger dosage of agents delivered intravenously increases the incidence of adverse events systemically and may even lead to interruption of the treatment.…”

Section: Application Of Intratumoral Immunotherapymentioning

confidence: 99%

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%

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

2023

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“…The development of new live imaging tools may improve injection reproducibility. Combinatorial approaches with intra-tumoral and intravenous treatment, or tumor ablation, are also being investigated and may represent a promising therapeutic alternative [ 109 ].…”

Section: Routes Of Administration For Therapeutic Antibodiesmentioning

confidence: 99%

Alternative Routes of Administration for Therapeutic Antibodies—State of the Art

2022

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Background: For the past two decades, there has been a huge expansion in the development of therapeutic antibodies, with 6 to 10 novel entities approved each year. Around 70% of these Abs are delivered through IV injection, a mode of administration allowing rapid and systemic delivery of the drug. However, according to the evidence presented in the literature, beyond the reduction of invasiveness, a better efficacy can be achieved with local delivery. Consequently, efforts have been made toward the development of innovative methods of administration, and in the formulation and engineering of novel Abs to improve their therapeutic index. Objective: This review presents an overview of the routes of administration used to deliver Abs, different from the IV route, whether approved or in the clinical evaluation stage. We provide a description of the physical and biological fundamentals for each route of administration, highlighting their relevance with examples of clinically-relevant Abs, and discussing their strengths and limitations. Methods: We reviewed and analyzed the current literature, published as of the 1 April 2022 using MEDLINE and EMBASE databases, as well as the FDA and EMA websites. Ongoing trials were identified using clinicaltrials.gov. Publications and data were identified using a list of general keywords. Conclusions: Apart from the most commonly used IV route, topical delivery of Abs has shown clinical successes, improving drug bioavailability and efficacy while reducing side-effects. However, additional research is necessary to understand the consequences of biological barriers associated with local delivery for Ab partitioning, in order to optimize delivery methods and devices, and to adapt Ab formulation to local delivery. Novel modes of administration for Abs might in fine allow a better support to patients, especially in the context of chronic diseases, as well as a reduction of the treatment cost.

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“…In previous preclinical studies, RFA and in situ administration of an immune-muco-adherent thermogel (IMT) containing macrophage colony-stimulating factor (GM-CSF) and BCG treated distant microscopic lesions in mice through a strong specific immune response that induced an abscopal effect. The immune escape of bulky lesions was reversible with the addition of a systemic PD-1 blockade [ 10 , 12 ]. Because BCG immunotherapy induces sepsis [ 13 ], live vaccines must be replaced with a safe adjuvant.…”

Section: Introductionmentioning

confidence: 99%

Radiofrequency Combined with Intratumoral Immunotherapy: Preclinical Results and Safety in Metastatic Colorectal Carcinoma

Seguin,

El Hajjam,

Legagneux

et al. 2024

Pharmaceutics

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Radiofrequency ablation (RFA) of cancer induces an anti-tumor immunity, which is insufficient to prevent recurrences. In mice, RFA–intratumoral immunotherapy by granulocyte–macrophage colony-stimulating factor (GM-CSF) and Bacillus Calmette-Guerin resulted in complete metastases regression. Infectious risk in human needs replacement of live vaccines. Intratumoral purified protein derivatives (PPD) have never been tested in digestive cancers, and the safety of intratumoral immunotherapy after RFA has not yet been validated in human models. We investigated the therapeutic efficacy of combined radiofrequency ablation (RFA) and intratumoral immunotherapy (ITI) using an immune-muco-adherent thermogel (IMT) in a mouse model of metastatic colorectal cancer (CRC) and the safety of this approach in a pig model. Intratumoral stability of the immunogel was assessed using magnetic resonance imaging (MRI) and bioluminescent imaging. Seventy-four CT26 tumor-bearing female BALB/c mice were treated with RFA either alone or in combination with intratumoral IMT. Regression of distant metastasis and survival were monitored for 60 days. Six pigs that received liver radiofrequency and intralesional IMT injections were followed for 15 days. Experimental gel embolisms were treated using an intravascular approach. Pertinent rheology of IMT was confirmed in tumors, by the signal stability during 3 days in MRI and 7 days in bioluminescence imaging. In mice, the abscopal effect of RFA–intratumoral immunotherapy resulted in regression of distant lesions completed at day 16 vs. a volume of 350 ± 99.3 mm3 in the RFA group at day 25 and a 10-fold survival rate at 60 days. In pigs, injection of immunogel in the liver RFA area was safe after volume adjustment without clinical, hematological, and liver biology disorder. Flow cytometry showed an early increase in CD3 TCR+T cells at D7 (p < 0.05) and a late decrease in CD29+-CD8 T cells at D15 (p < 0.05), reflecting the inflammation status changes. Systemic GM-CSF release was not detectable. Experimental caval and pulmonary thermogel embolisms were treated by percutaneous catheterism and cold serum infusion. RFA–intratumoral immunotherapy as efficient and safe mini-invasive interventional oncology is able to improve ablative treatment of colorectal liver metastases.

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Intratumoral Immunotherapy and Tumor Ablation: A Local Approach with Broad Potential

Cited by 9 publications

References 61 publications

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

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

Alternative Routes of Administration for Therapeutic Antibodies—State of the Art

Radiofrequency Combined with Intratumoral Immunotherapy: Preclinical Results and Safety in Metastatic Colorectal Carcinoma

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