Abstract 956: Tumor treating fields (TTFields) elicit an anti-tumor immune response and in combination enhance anti-PD-1 treatment efficacy

AbstractTumor-treating fields (TTFields) are alternating fields (200 kHz) used to treat glioblastoma (GBM), which is one of the deadliest cancer diseases of all. Glioblastoma is a type of malignant brain cancer, which causes significant neurological deterioration and reduced quality of life, and for which there is currently no curative treatment. TTFields were recently introduced as a novel treatment modality in addition to surgery, radiation therapy, and chemotherapy. The fields are induced noninvasively using two pairs of electrode arrays placed on the scalp. Due to low electrical conductivity, significant currents are shielded from the intracranial space, potentially compromising treatment efficacy. Recently, skull remodeling surgery (SR-surgery) was proposed to address this issue. SR-surgery comprises the formation of skull defects or thinning of the skull over the tumor to redirect currents toward the pathology and focally enhance the field intensity. Safety and feasibility of this concept were validated in a clinical phase 1 trial (OptimalTTF-1), which also indicated promising survival benefits. This chapter describes the FE methods used in the OptimalTTF-1 trial to plan SR-surgery and assess treatment efficacy. We will not present detailed modeling results from the trial but rather general concepts of model development and field calculations. Readers are kindly referred to Wenger et al. [1] for a more general overview of the clinical implications and applications of TTFields modeling.

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IgG Responses to Tissue-Associated Antigens as Biomarkers of Immunological Treatment Efficacy

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/454861 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Heath A. Smith ◽

Brett B. Maricque ◽

John Eberhardt ◽

Benjamin Petersen ◽

James L. Gulley ◽

...

Keyword(s):

Prostate Cancer ◽

Immune Response ◽

Cancer Patients ◽

Dna Vaccine ◽

Predictive Models ◽

Treatment Efficacy ◽

Bayesian Belief Network ◽

Androgen Deprivation ◽

Immunological Treatment ◽

Current Report

We previously demonstrated that IgG responses to a panel of 126 prostate tissue-associated antigens are common in patients with prostate cancer. In the current report we questioned whether changes in IgG responses to this panel might be used as a measure of immune response, and potentially antigen spread, following prostate cancer-directed immune-active therapies. Sera were obtained from prostate cancer patients prior to and three months following treatment with androgen deprivation therapy (), a poxviral vaccine (), and a DNA vaccine (). Changes in IgG responses to individual antigens were identified by phage immunoblot. Patterns of IgG recognition following three months of treatment were evaluated using a machine-learned Bayesian Belief Network (ML-BBN). We found that different antigens were recognized following androgen deprivation compared with vaccine therapies. While the number of clinical responders was low in the vaccine-treated populations, we demonstrate that ML-BBN can be used to develop potentially predictive models.

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The 6th R of Radiobiology: Reactivation of Anti-Tumor Immune Response

Cancers ◽

10.3390/cancers11060860 ◽

2019 ◽

Vol 11 (6) ◽

pp. 860 ◽

Cited By ~ 11

Author(s):

Boustani ◽

Grapin ◽

Laurent ◽

Apetoh ◽

Mirjolet

Keyword(s):

Immune Response ◽

Radiation Therapy ◽

Cyclic Gmp ◽

Treatment Efficacy ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Abscopal Effect ◽

Intrinsic Radiosensitivity ◽

Immunomodulatory Properties ◽

Review Current

Historically, the 4Rs and then the 5Rs of radiobiology explained the effect of radiation therapy (RT) fractionation on the treatment efficacy. These 5Rs are: Repair, Redistribution, Reoxygenation, Repopulation and, more recently, intrinsic Radiosensitivity. Advances in radiobiology have demonstrated that RT is able to modify the tumor micro environment (TME) and to induce a local and systemic (abscopal effect) immune response. Conversely, RT is able to increase some immunosuppressive barriers, which can lead to tumor radioresistance. Fractionation and dose can affect the immunomodulatory properties of RT. Here, we review how fractionation, dose and timing shape the RT-induced anti-tumor immune response and the therapeutic effect of RT. We discuss how immunomodulators targeting immune checkpoint inhibitors and the cGAS/STING (cyclic GMP-AMP Synthase/Stimulator of Interferon Genes) pathway can be successfully combined with RT. We then review current trials evaluating the RT/Immunotherapy combination efficacy and suggest new innovative associations of RT with immunotherapies currently used in clinic or in development with strategic schedule administration (fractionation, dose, and timing) to reverse immune-related radioresistance. Overall, our work will present the existing evidence supporting the claim that the reactivation of the anti-tumor immune response can be regarded as the 6th R of Radiobiology.

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