Assessment of Image-Guided Intratumoral Delivery of Immunotherapeutics in Patients With Cancer

JAMA Network Open. 2020;3(7):

The purpose of this study was to address current knowledge gaps in image-guided techniques for intratumoral immunotherapy delivery and the safety of these interventions. The authors concluded that intratumoral delivery of immunotherapies is technically feasible with low major complication rates.

Regression of metastatic cancer and abscopal effects following in situ vaccination by cryosurgical tumor cell lysis and intratumoral immunotherapy: A case series

Poster #6540
Presented at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II, June 22-24

This poster reports the evaluation of the efficacy and safety of an in situ cancer vaccination method for the treatment of aggressive solid tumors, with an initial focus on metastatic prostate cancer (mPCa). The method utilized cryosurgical cell lysis coupled with intratumoral immunotherapy. The therapy was well tolerated and demonstrated a 50% complete response in evaluable patients.

New pathways in immune stimulation: targeting OX40

ESMO Open 2020;5:e000573.

Discusses the rationale of OX40 targeting, highlighting the combination of OX40-directed therapies with different anticancer agents as a potential strategy to foster the immune system against malignant phenotypes.

The Immunotherapy Revolution: The Best New Hope For Saving Cancer Patients’ Lives

Jason R. Williams, M.D. (2019) 

As one of the pioneers in immunotherapy, Dr. Williams, introduces and reviews his new approach to cancer treatment. He explains how he performed the world’s first ablation procedure combined with an intratumoral injection of a specific combination of immunotherapy agents, thus leveraging the actual process of ablation as an immunotherapy agent itself.

Cryoablation and immunotherapy: an overview of evidence on its synergy

Insights into Imaging (2019) 10:53

In this review, the authors outline the current evidence for the combination of cryoablation with immunotherapy to treat cancer.

Starting the fight in the tumor:
expert recommendations for the development of human intratumoral immunotherapy (HIT-IT)

Annals of Oncology 29: 2163–2174, 2018

Summarizes recommendations from the 2018 ESMO meeting, which focused exclusively on the human intratumoral injection/delivery (HIT-IT) of immuno-stimulatory agents. The goal was to provide a reference document, endorsed by the panel members that could provide guidance for future HIT-IT clinical trials.

Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal
Effect for Advanced Cancers

Frontiers in Oncology. 8:85, 2018

Reviews preclinical and clinical evidence that exists for the complementary roles for CTLA-4 and PD-1 antagonists in regulating adaptive immunity, demonstrating that combination immunotherapy followed by cryosurgery provides a more targeted immune response to distant lesions, a phenomenon known as the abscopal effect.

Intratumoral immunotherapy:
using the tumor as the remedy

Annals of Oncology 28 (Supplement 12): xii33–xii43, 2017

Reviews the potential for intratumoral immunotherapy as a therapeutic strategy to use the tumor as its own vaccine.

Image guided cryoablation of cancer with intratumoral injection of anti-CTLA-4 and PD-1 immune check-point inhibitors

Journal for Immunotherapy of Cancer 2015, 3(Suppl 2):P142

This poster is from the 30th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2015). It describes proof of concept data using a new therapy that combines cryoablation with intratumoral injection of anti-PD-1 and anti-CTLA-4.

Cancer immunotherapy using tumor cryoablation

Immunotherapy (2014) 6(1), 85–93

This article reviews the preclinical and clinical evidence and discusses the
mechanism of the antitumor immune response generated by cryoablation. The rationale and evidence behind several immunotherapy approaches that can be combined with cryoablation to devise a cryoimmunotherapeutic strategy with a potential to impact the progression of metastatic disease are described.

Intratumoral Immunization: A New Paradigm for Cancer Therapy

Clinical Cancer Research. 2014 April 1; 20(7): 1747–1756.

Reviews challenges of systemic immunotherapy as well as pre-clinical and clinical evidence that a therapeutic systemic anti-tumor immune response can be generated upon intra-tumoral immunomodulation.

Intratumoral Anti-CTLA-4 Therapy: Enhancing Efficacy While Avoiding Toxicity

Clinical Cancer Research. 2013 October 1; 19(19)

In this issue of Clinical Cancer Research, Marabelle and colleagues show that the peri-tumoral delivery of low doses of an anti-CTLA-4 monoclonal antibody can generate a systemic antitumor immune response able to prevent the growth of a distant subsequent tumor challenge.

Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy

Cancer Research. 2012 January 15; 72(2): 430–439.

This study reviews preclinical proof of concept in the TRAMP-C2 mouse model of prostate cancer that CTLA-4 blockade cooperates with cryoablation of a primary tumor to prevent the outgrowth of secondary tumors seeded by challenge at a distant site.

Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction

Vaccine 30 (2012) 737– 744

This article reports the testing and ability of various peri-tumoral non-microbial vaccine adjuvants to modulate the immune response following cryoablation.

Combined Dendritic Cell Cryotherapy of Tumor Induces Systemic Antimetastatic Immunity

Clin Cancer Res 2005;11(13) July 1, 2005

Machlenkin et al were the first to report systemic antimetastatic immunity after using cryotherapy of tumors combined with subsequent in situ immunotherapy with autologous unmodified immature dendritic cells.

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