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Literature DB >> 34210684

Organoid Platform in Preclinical Investigation of Personalized Immunotherapy Efficacy in Appendiceal Cancer: Feasibility Study.

Steven D Forsythe^1,2,3, Richard A Erali^1,2,4, Shyama Sasikumar^1,2, Preston Laney^1,2, Ethan Shelkey^1,2, Ralph D'Agostino^5,6, Lance D Miller^1,3,5, Perry Shen^4,5, Edward A Levine^4,5, Shay Soker^1,2,3,5, Konstantinos I Votanopoulos^7,2,4,5.

Abstract

PURPOSE: Immunotherapy efficacy data on appendiceal cancer from clinical trials does not exist, due to appendiceal cancer incidence of 0.97 per 100,000. The goal of this study was to preclinically explore the application of immunotherapy in treating appendiceal cancer in a personalized organoid model. EXPERIMENTAL
DESIGN: Patient tumor organoids (PTO) were fabricated using unsorted tumor cells with and without enrichment with patient-matched immune components derived from peripheral blood leukocytes, spleen, or lymph nodes [immune-enhanced PTOs (iPTO)]. Organoids were cultured for 7 days, followed by treatment with immunotherapy (pembrolizumab, ipilimumab, nivolumab), and assessed for treatment efficacy.
RESULTS: Between September 2019 and May 2021, 26 patients were enrolled in the study. Successful testing was conducted in 19 of 26 (73.1%) patients, with 13 of 19 (68.4%) and 6 of 19 (31.6%) patients having low-grade appendiceal (LGA) and high-grade appendiceal (HGA) primaries, respectively. Immunotherapy response, with increased expression of granzyme B and cleaved caspase 3 and decreased expression of CK20 and ATP activity, was exhibited in 4 of 19 (21.1%) pembrolizumab-treated and 2 of 19 (10.5%) nivolumab-treated iPTOs. Post-immunotherapy cellular viability, in responding HGA organoids to pembrolizumab, decreased to less than 15% (P < 0.05). LGA iPTO treatment responses were observed in pembrolizumab and nivolumab, with an 8%-47.4% (P < 0.05) viability compared with controls. Ipilimumab showed no efficacy in the examined cohort.
CONCLUSIONS: Immunotherapy shows measurable efficacy in appendiceal cancer organoids. Information derived from immunocompetent organoids may be applied in selecting patients for clinical trial enrollment in rare diseases where preclinical models of disease are lacking. ©2021 American Association for Cancer Research.

Entities: Chemical

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Year: 2021 PMID： 34210684 PMCID： PMC8720262 DOI： 10.1158/1078-0432.CCR-21-0982

Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 13.801

16 in total

1. Model of Patient-Specific Immune-Enhanced Organoids for Immunotherapy Screening: Feasibility Study.

Authors: Konstantinos I Votanopoulos; Steven Forsythe; Hemamylammal Sivakumar; Andrea Mazzocchi; Julio Aleman; Lance Miller; Edward Levine; Pierre Triozzi; Aleksander Skardal
Journal: Ann Surg Oncol Date: 2019-12-19 Impact factor: 5.344

2. Appendiceal Cancer Patient-Specific Tumor Organoid Model for Predicting Chemotherapy Efficacy Prior to Initiation of Treatment: A Feasibility Study.

Authors: Konstantinos I Votanopoulos; Andrea Mazzocchi; Hemamylammal Sivakumar; Steven Forsythe; Julio Aleman; Edward A Levine; Aleksander Skardal
Journal: Ann Surg Oncol Date: 2018-11-09 Impact factor: 5.344

3. Pembrolizumab versus Ipilimumab in Advanced Melanoma.

Authors: Caroline Robert; Jacob Schachter; Georgina V Long; Ana Arance; Jean Jacques Grob; Laurent Mortier; Adil Daud; Matteo S Carlino; Catriona McNeil; Michal Lotem; James Larkin; Paul Lorigan; Bart Neyns; Christian U Blank; Omid Hamid; Christine Mateus; Ronnie Shapira-Frommer; Michele Kosh; Honghong Zhou; Nageatte Ibrahim; Scot Ebbinghaus; Antoni Ribas
Journal: N Engl J Med Date: 2015-04-19 Impact factor: 91.245

4. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

Authors: Dung T Le; Jennifer N Durham; Kellie N Smith; Hao Wang; Bjarne R Bartlett; Laveet K Aulakh; Steve Lu; Holly Kemberling; Cara Wilt; Brandon S Luber; Fay Wong; Nilofer S Azad; Agnieszka A Rucki; Dan Laheru; Ross Donehower; Atif Zaheer; George A Fisher; Todd S Crocenzi; James J Lee; Tim F Greten; Austin G Duffy; Kristen K Ciombor; Aleksandra D Eyring; Bao H Lam; Andrew Joe; S Peter Kang; Matthias Holdhoff; Ludmila Danilova; Leslie Cope; Christian Meyer; Shibin Zhou; Richard M Goldberg; Deborah K Armstrong; Katherine M Bever; Amanda N Fader; Janis Taube; Franck Housseau; David Spetzler; Nianqing Xiao; Drew M Pardoll; Nickolas Papadopoulos; Kenneth W Kinzler; James R Eshleman; Bert Vogelstein; Robert A Anders; Luis A Diaz
Journal: Science Date: 2017-06-08 Impact factor: 47.728

5. Molecular Profiling of Appendiceal Adenocarcinoma and Comparison with Right-sided and Left-sided Colorectal Cancer.

Authors: Ryuma Tokunaga; Joanne Xiu; Curtis Johnston; Richard M Goldberg; Philip A Philip; Andreas Seeber; Madiha Naseem; Jae Ho Lo; Hiroyuki Arai; Francesca Battaglin; Alberto Puccini; Martin D Berger; Shivani Soni; Wu Zhang; Jimmy J Hwang; Anthony F Shields; John L Marshall; Hideo Baba; W Michael Korn; Heinz-Josef Lenz
Journal: Clin Cancer Res Date: 2019-01-28 Impact factor: 12.531

Review 6. Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable.

Authors: Vinay Prasad; Victoria Kaestner
Journal: Semin Oncol Date: 2017-07-13 Impact factor: 4.929

7. The Chicago Consensus on Peritoneal Surface Malignancies: Management of Appendiceal Neoplasms.

Authors:
Journal: Ann Surg Oncol Date: 2020-04-13 Impact factor: 5.344

8. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial.

Authors: Charles S Fuchs; Toshihiko Doi; Raymond W Jang; Kei Muro; Taroh Satoh; Manuela Machado; Weijing Sun; Shadia I Jalal; Manish A Shah; Jean-Phillipe Metges; Marcelo Garrido; Talia Golan; Mario Mandala; Zev A Wainberg; Daniel V Catenacci; Atsushi Ohtsu; Kohei Shitara; Ravit Geva; Jonathan Bleeker; Andrew H Ko; Geoffrey Ku; Philip Philip; Peter C Enzinger; Yung-Jue Bang; Diane Levitan; Jiangdian Wang; Minori Rosales; Rita P Dalal; Harry H Yoon
Journal: JAMA Oncol Date: 2018-05-10 Impact factor: 31.777

9. In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening.

Authors: Andrea R Mazzocchi; Shiny A P Rajan; Konstantinos I Votanopoulos; Adam R Hall; Aleksander Skardal
Journal: Sci Rep Date: 2018-02-13 Impact factor: 4.379

10. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.

Authors: Georgios Vlachogiannis; Somaieh Hedayat; Alexandra Vatsiou; Yann Jamin; Javier Fernández-Mateos; Khurum Khan; Andrea Lampis; Katherine Eason; Ian Huntingford; Rosemary Burke; Mihaela Rata; Dow-Mu Koh; Nina Tunariu; David Collins; Sanna Hulkki-Wilson; Chanthirika Ragulan; Inmaculada Spiteri; Sing Yu Moorcraft; Ian Chau; Sheela Rao; David Watkins; Nicos Fotiadis; Maria Bali; Mahnaz Darvish-Damavandi; Hazel Lote; Zakaria Eltahir; Elizabeth C Smyth; Ruwaida Begum; Paul A Clarke; Jens C Hahne; Mitchell Dowsett; Johann de Bono; Paul Workman; Anguraj Sadanandam; Matteo Fassan; Owen J Sansom; Suzanne Eccles; Naureen Starling; Chiara Braconi; Andrea Sottoriva; Simon P Robinson; David Cunningham; Nicola Valeri
Journal: Science Date: 2018-02-23 Impact factor: 47.728

10 in total

1. Patient-Specific Sarcoma Organoids for Personalized Translational Research: Unification of the Operating Room with Rare Cancer Research and Clinical Implications.

Authors: Steven D Forsythe; Hemamylammal Sivakumar; Richard A Erali; Nadeem Wajih; Wencheng Li; Perry Shen; Edward A Levine; Katherine E Miller; Aleksander Skardal; Konstantinos I Votanopoulos
Journal: Ann Surg Oncol Date: 2022-07-03 Impact factor: 4.339

Organoid Platform in Preclinical Investigation of Personalized Immunotherapy Efficacy in Appendiceal Cancer: Feasibility Study.

1. Model of Patient-Specific Immune-Enhanced Organoids for Immunotherapy Screening: Feasibility Study.

2. Appendiceal Cancer Patient-Specific Tumor Organoid Model for Predicting Chemotherapy Efficacy Prior to Initiation of Treatment: A Feasibility Study.

3. Pembrolizumab versus Ipilimumab in Advanced Melanoma.

4. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

5. Molecular Profiling of Appendiceal Adenocarcinoma and Comparison with Right-sided and Left-sided Colorectal Cancer.

Review 6. Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable.

7. The Chicago Consensus on Peritoneal Surface Malignancies: Management of Appendiceal Neoplasms.

8. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial.

9. In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening.

10. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.

1. Patient-Specific Sarcoma Organoids for Personalized Translational Research: Unification of the Operating Room with Rare Cancer Research and Clinical Implications.

2. ASO Author Reflections: Sarcoma Organoids: Neutralizing the Word "Rare" in Rare Cancers.

3. Immuno-reactive cancer organoid model to assess effects of the microbiome on cancer immunotherapy.

Review 4. Application of Patient-Derived Cancer Organoids to Personalized Medicine.

Review 5. Organoid Models for Precision Cancer Immunotherapy.

6. Establishment of gastric signet ring cell carcinoma organoid for the therapeutic drug testing.

Review 7. Engineered Microphysiological Systems for Testing Effectiveness of Cell-Based Cancer Immunotherapies.

8. Application of immune enhanced organoids in modeling personalized Merkel cell carcinoma research.

Review 9. Applications of human organoids in the personalized treatment for digestive diseases.

Review 10. Advances in the application of 3D tumor models in precision oncology and drug screening.