#TwittIR: Understanding and Establishing a Twitter Ecosystem for Interventional Radiologists and Their Practices.

The use of social media among interventional radiologists is increasing, with Twitter receiving the most attention. Twitter is an ideal forum for open exchange of ideas from around the world. However, it is important for Twitter users to gain a rudimentary understanding of the many potential communication pathways to connect with other users. An intentional approach to Twitter is vital to efficient and successful use. This article describes several common communication pathways that can be utilized by physicians in their interventional radiology practice

Abstract A018: Effects of Toca 511 and Toca FC on tumor microenvironment and peripheral blood populations in patients with advanced malignancies

Abstract Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector that selectively infects cancer cells due to cell division requirements for virus integration into the genome, and defects in innate and adaptive immune responses found in malignant tissues that support virus replication. Toca 511 spreads through cancer cells and stably delivers optimized yeast cytosine deaminase (CD) that, upon administration of the prodrug, Toca FC (an investigational, extended-release version of 5-fluorocytosine [5-FC]), converts 5-FC into 5-fluorouracil (5-FU). 5-FU kills infected dividing cancer cells and diffuses to and kills surrounding cells in the tumor microenvironment, including immunosuppressive myeloid cells. In animal models, this depletion of immunosuppressive myeloid cells leads to therapeutically active immunity against tumors. A similarly derived antitumor response may occur in cancer patients, as local injection of Toca 511 into the tumor bed after resection of recurrent high-grade glioma followed by treatment with Toca FC has been associated with prolonged survival and durable complete responses (median duration of follow-up: 37.4+ months); responses were delayed in onset, consistent with time to response for immuno-oncology agents. The current phase 1b, multicenter, open-label study (Toca 6; NCT02576665) is designed to investigate changes in immune activity after treatment with Toca 511 and Toca FC in patients with advanced malignancies. Toca 511 is administered intravenously (IV) daily for 3 days and then as a single injection into metastatic or recurrent tumor. Oral Toca FC is started ~4 weeks later and repeated every 4-6 weeks. Biopsies are obtained prior to and following exposure to Toca 511 and Toca FC treatment to evaluate changes in immune activity, and peripheral blood is obtained contemporaneously for evaluation. The study has enrolled 19 patients to date (colorectal cancer: 15; sarcoma: 2; non-small cell lung and pancreas cancer: 1 each). Treatment has been well tolerated. Viral RNA, DNA, and CD protein expression are observed in tumor after IV delivery of Toca 511. We plan to report on tumor microenvironment remodeling that follows treatment with Toca 511 and Toca FC. Infiltrating T-cell subpopulations, B cells, and monocytes quantified by immunofluorescence from stained formalin-fixed, paraffin-embedded samples will be presented. Additionally, changes in peripheral blood, including T-cell effector, helper/memory, and regulatory populations, and myeloid lineage cells following exposure to Toca 511 alone and following subsequent exposure to Toca FC will be reported. Data from this study will inform future development of Toca 511 and Toca FC alone or in combination with other therapies in patients with solid tumors. Citation Format: Jaime Merchan, Jordi Rodon, Derek Ostertag, Shree Venkat, Arthur Donahue, Peder Horner, Dalissa Tijera, Thian Kheoh, Douglas J. Jolly, Harry E. Gruber, Jolene S. Shorr, Gerald S. Falchook. Effects of Toca 511 and Toca FC on tumor microenvironment and peripheral blood populations in patients with advanced malignancies [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A018

Immune modulation after Toca 511 and Toca FC treatment of colorectal cancer patients

186 Background: Toca 511 (vocimagene amiretrorepvec) is a cancer-selective, retroviral replicating vector encoding yeast cytosine deaminase that converts 5-fluorocytosine (5-FC) into 5-fluorouracil in the tumor microenvironment (TME). In animal models, Toca 511 and 5-FC kill dividing cancer and nearby immunosuppressive cells, leading to antitumor immune activity. A Phase 1 study of Toca 511 & Toca FC (extended-release 5-FC) in patients with recurrent high grade glioma revealed results consistent with this proposed mechanism. A Phase 3 trial is ongoing. Methods: Toca 6 (NCT02576665) is a Phase 1b, single-arm, multicenter study designed to investigate immunological changes after Toca 511 & Toca FC treatment in patients with advanced solid tumors, including colorectal cancer (CRC). Patients received intravenous (IV) Toca 511 for 3 days, and underwent biopsy of metastatic tumor before and ~ 4 weeks after starting oral Toca FC. Toca FC was repeated every 4-6 weeks. Peripheral blood mononuclear cells and tumor biopsies were evaluated for treatment related immune responses. Results: 17 CRC patients with a median 5 lines of prior chemotherapy were enrolled. At last data cut-off, 9 patients were alive and the median overall survival was 9.4 months. A patient receiving concomitant panitumumab had a partial response. IV Toca 511 led to viral expression in tumor, which decreased post-Toca FC while maintaining a reservoir of virus in the remaining tumor. T cells shifted from naïve to effector phenotypes, CD4 memory T cells expanded, and/or B cells increased after Toca FC treatment in 36% of patients. Marked changes in tumor infiltrating cells (CD11b myeloid cells, Tregs, exhausted T cells and CD8 T cells) occurred after Toca FC treatment. Treatment has been generally well tolerated. We also plan to report insights gained from RNA analysis of TME and update on clinical finding. Conclusions: Clinical data suggest a signal of activity in these heavily pretreated CRC patients warranting further exploration. IV Toca 511 administration showed viral infection of CRC metastatic tumor. Toca 511 & Toca FC may be associated with T cell mediated immune activity in peripheral blood and metastatic tumor, consistent with pre-clinical data in multiple tumor types. Clinical trial information: NCT02576665

#TwittIR: Understanding and Establishing a Twitter Ecosystem for Interventional Radiologists and Their Practices

The use of social media among interventional radiologists is increasing, with Twitter receiving the most attention. Twitter is an ideal forum for open exchange of ideas from around the world. However, it is important for Twitter users to gain a rudimentary understanding of the many potential communication pathways to connect with other users. An intentional approach to Twitter is vital to efficient and successful use. This article describes several common communication pathways that can be utilized by physicians in their interventional radiology practice