A Pilot Study of Consolidative Immunotherapy in Patients with High-Risk Pediatric Sarcomas
Crystal L. Mackall,Eunice H. Rhee,Elizabeth J. Read,Hanh Khuu,Susan F. Leitman,Donna Bernstein,Merertu Tesso,Lauren M. Long,David J. Grindler,Margret E. Merino,William Kopp,Maria Tsokos,Jay A. Berzofsky,Lee J. Helman +13 more
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TLDR
The robust influenza immune responses observed suggest that postchemotherapy immune incompetence will not fundamentally limit this approach for integrating immunotherapy into a multimodal regimen for chemoresponsive cancer.Abstract:
Purpose: Patients with metastatic or recurrent Ewing’s sarcoma family of tumors and alveolar rhabdomyosarcoma have Experimental Design: Fifty-two patients with translocation positive, recurrent, or metastatic Ewing’s sarcoma family of tumors or alveolar rhabdomyosarcoma underwent prechemotherapy cell harvest via apheresis for potential receipt of immunotherapy. Following completion of standard multimodal therapy, 30 patients ultimately initiated immunotherapy and were sequentially assigned to three cohorts. All cohorts received autologous T cells, influenza vaccinations, and dendritic cells pulsed with peptides derived from tumor-specific translocation breakpoints and E7, a peptide known to bind HLA-A2. Cohort 1 received moderate-dose recombinant human interleukin-2 (rhIL-2), cohort 2 received low-dose rhIL-2, and cohort 3 did not receive rhIL-2. Results: All immunotherapy recipients generated influenza-specific immune responses, whereas immune responses to the translocation breakpoint peptides occurred in 39%, and only 25% of HLA-A2 + patients developed E7-specific responses. Toxicity was minimal. Intention-to-treat analysis revealed a 31% 5-year overall survival for all patients apheresed (median potential follow-up 7.3 years) with a 43% 5-year overall survival for patients initiating immunotherapy. Conclusions: Consolidative immunotherapy is a scientifically based and clinically practical approach for integrating immunotherapy into a multimodal regimen for chemoresponsive cancer. Patients receiving immunotherapy experienced minimal toxicity and favorable survival. The robust influenza immune responses observed suggest that postchemotherapy immune incompetence will not fundamentally limit this approach. Future studies will seek to increase efficacy by using more immunogenic antigens and more potent dendritic cells.read more
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The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research
Martin A. Cheever,Martin A. Cheever,James P. Allison,Andrea S. Ferris,Olivera J. Finn,Benjamin M. Hastings,Toby T. Hecht,Ira Mellman,Sheila A. Prindiville,Jaye L. Viner,Louis M. Weiner,Lynn M. Matrisian +11 more
TL;DR: The findings reflect the current status of the cancer vaccine field, highlight the possibility that additional organized efforts and funding would accelerate the development of therapeutically effective cancer vaccines, and accentuate the need for prioritization.
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Alternative tumour-specific antigens.
Christof C. Smith,Sara R. Selitsky,Shengjie Chai,Paul M. Armistead,Benjamin G. Vincent,Jonathan S. Serody +5 more
TL;DR: Examples of TSAs alternative to the traditional single-nucleotide variant neoantigens are provided and details about the novel computational tools used to identify them are provided, with the view to broaden the number of targetable antigens that can be used for cancer vaccine development.
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Immunotherapy for osteosarcoma: Fundamental mechanism, rationale, and recent breakthroughs.
TL;DR: A review of recent advances in immunotherapy in osteosarcoma and discuss the mechanisms and status of immunotherapies in both preclinical and clinical trials as well as future therapies on the horizon is presented in this article.
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Identifying and Targeting Human Tumor Antigens for T Cell-Based Immunotherapy of Solid Tumors.
Vid Leko,Steven A. Rosenberg +1 more
TL;DR: Molecular identification of different tumor antigen types, and the clinical safety and efficacy of targeting them with immunotherapy, are discussed and strategies to increase the efficacy and availability of antigen-directed immunotherapies for treatment of patients with metastatic cancer are suggested.
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Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer
Hua Zhang,Irena Maric,Michael DiPrima,Javed Khan,Rimas J. Orentas,Rosandra N. Kaplan,Crystal L. Mackall +6 more
TL;DR: A novel subset of cancer-induced myeloid-derived suppressor cells are described, which bear the phenotypic and functional hallmarks of fibrocytes but mediate immune suppression and may contribute to tumor progression via both immune evasion and angiogenesis.
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TL;DR: The adoptive transfer of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen resulted in the persistent clonal repopulation of T cells in cancer patients, leading to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction.
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Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
Beatrice Thurner,Ina Haendle,Claudia Röder,Detlef Dieckmann,Petra Keikavoussi,Helmut Jonuleit,Armin Bender,Christian Maczek,Doris Schreiner,Peter von den Driesch,Eva B. Bröcker,Ralph M. Steinman,Alexander Enk,Eckhart Kämpgen,Gerold Schuler +14 more
TL;DR: The principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer is proved and evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression is provided.
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