Article
Immunology
Vera Portillo, Stavroula Masouridi-Levrat, Lena Royston, Sabine Yerly, Manuel Schibler, Maria Mappoura, Sarah Morin, Federica Giannotti, Anne-Claire Mamez, Christian van Delden, Yves Chalandon, Dionysios Neofytos
Summary: Positive CMV serology in allogeneic hematopoietic cell transplant recipients (allo-HCTRs) may be false-positive due to transfusion-associated passive immunity. Reclassifying CMV status can help accurately assess the risk of CMV infection in these patients.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Maite Alvarez, Antonio Pierini, Federico Simonetta, Jeanette Baker, Kristina Maas-Bauer, Toshihito Hirai, Robert S. Negrin
Summary: Allogeneic hematopoietic cell transplantation is an effective treatment option for hematological malignancies, but often results in severe toxicities. Less aggressive alternatives like NMAC and RIC have limitations including increased cancer relapse and limited persistence of donor chimerism. Strategies for accelerated and more durable donor engraftment are still needed.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Infectious Diseases
Fatima Allaw, Sara F. Haddad, Johnny Zakhour, Souha S. Kanj
Summary: Cytomegalovirus (CMV) is a common infection in immunocompromised patients, especially those undergoing allo-HSCT. Recent management strategies include pre-emptive treatment with frequent CMV PCR monitoring and the use of new drugs like letermovir. Treatment of CMV disease is challenging due to drug resistance, but promising results have been seen with maribavir and other alternative treatments such as immunotherapy, artesunate, and leflunomide.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Hematology
Amanda M. Casto, Sachiko Seo, David M. Levine, Barry E. Storer, Xinyuan Dong, John A. Hansen, Michael Boeckh, Paul J. Martin
Summary: This study found that only the donor ABCB1 gene variant was associated with CMV reactivation after allogeneic hematopoietic cell transplantation. Other genetic variants previously linked to CMV phenotypes did not significantly alter the risk for CMV reactivation or disease post-transplant.
Article
Oncology
Raynier Devillier, Boris Calmels, Sophie Guia, Mohammed Taha, Cyril Fauriat, Bechara Mfarrej, Geoffroy Venton, Eric Vivier, Daniel Olive, Christian Chabannon, Didier Blaise, Sophie Ugolini
Summary: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective curative option for high-risk hematologic malignancies, but disease recurrence remains a critical issue. NK cell-based immunotherapies offer a promising approach to enhance anti-tumor effects without triggering graft-versus-host disease. This clinical trial demonstrates the safety and potential efficacy of prophylactic donor-derived IL-2 activated NK cell infusion after allo-HSCT for patients with hematologic malignancies.
Article
Immunology
Jintao Xia, Xuejie Li, Genyong Gui, Jian Wu, Shengnan Gong, Yuxin Shang, Jun Fan
Summary: This study evaluated the early immune response of recipients with disparate HCMV outcomes and found that HCMV-specific IFN-gamma secreting cells, HCMV IgG, and absolute lymphocyte count could represent the humoral and cellular immune response. Early monitoring of these immune markers could enable prediction of HCMV outcomes posttransplant and assessment of the severity of HCMV DNAemia.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Huiru Wang, Huilan Liu, Li Zhou, Dongyao Wang, Shushu Wang, Qian Liu, Yun Wu, Meijuan Tu, Zimin Sun, Xiaohu Zheng, Binqing Fu, Baolong Wang, Haiming Wei
Summary: This study compared the immune cells of patients with controlled and uncontrolled CMV infection after allo-HSCT. It found that patients with uncontrolled infection had insufficient B-cells due to impaired B-cell reconstitution. In contrast, patients with controlled infection had reconstructed B-cells showing mature B-cell characteristics and enrichment of CMV-associated B-cell receptors. Additionally, the controlled infection group had higher levels of anti-CMV-specific immunoglobulin G (IgG) in their serum, which could effectively inhibit CMV infection. These findings highlight the importance of B-cells and anti-CMV-specific neutralizing IgGs in controlling CMV infection post-allo-HSCT and suggest their potential as a supplementary treatment for improved outcomes.
Article
Cell Biology
Kristina M. Geiger, Michael Manoharan, Rachel Coombs, Kathya Arana, Chan-Su Park, Angus Y. Lee, Nilabh Shastri, Ellen A. Robey, Laurent Coscoy
Summary: The endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP) plays a critical role in shaping the peptide-MHC I repertoire and maintaining immune surveillance. Murine cytomegalovirus (MCMV) modulates ERAAP during infection, leading to Qa-1b-restricted QFL T cell proliferation, which reduces viral load and highlights potential targets for anti-viral therapies.
Article
Biophysics
Takehiko Mori, Taku Kikuchi, Miki Koh, Yuya Koda, Rie Yamazaki, Masatoshi Sakurai, Yohei Tomita, Yoko Ozawa, Sumiko Kohashi, Ryohei Abe, Masuho Saburi, Jun Kato
Summary: This study retrospectively evaluated the incidence and characteristics of CMV retinitis in recipients of allogeneic HSCT. The median onset of CMV retinitis was day 34 post transplant, with a cumulative incidence of 2.5% at 6 months. Active ophthalmological screening based on symptoms and CMV infection monitoring contributes to the early diagnosis of CMV retinitis.
BONE MARROW TRANSPLANTATION
(2021)
Review
Immunology
Chieh-Lin Jerry Teng, Po-Nan Wang, Yee-Chun Chen, Bor-Sheng Ko
Summary: CMV infection is a common and severe complication of allo-HSCT in Taiwan due to high CMV seropositivity in the population. A CMV management strategy focusing on monitoring, prophylaxis, and treatment is proposed, including weekly monitoring with the COBAS (R) AmpliPrep system, a 14-week prophylactic course of letermovir for allo-HSCT recipients, and preemptive ganciclovir therapy when CMV viral load exceeds 1000 copies/mL. Limited availability of foscarnet is a crucial issue for patients not responsive to ganciclovir in Taiwan.
JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION
(2021)
Article
Medicine, General & Internal
Nan Su, Zhenghua Liu, Peng Sun, Feng Gu, Xiaojing Yan, Dali Cai
Summary: This article reports a case of drug-resistant CMV infection after allo-HSCT and describes successful treatment with intravenous infusion of CMV-CTLs.
FRONTIERS IN MEDICINE
(2022)
Article
Oncology
Elena Kum, Gabriele Jagelaviciute, Edward Li, Kenneth Williams, Santhosh Thyagu, Warren Fingrut
Summary: The article tells the story of a Canadian stem cell recipient who underwent transplantation from a matched unrelated donor for refractory chronic myelogenous leukemia, showcasing different perspectives and encouraging people to become donors.
Review
Oncology
Hana Andrlova, Marcel R. M. van den Brink, Kate A. Markey
Summary: Allogeneic hematopoietic cell transplantation (allo-HCT) is a treatment for hematologic malignancies, but its broader implementation is limited by high rates of complications and mortality. Reconstitution of the immune system is crucial for good long-term outcomes. Unconventional T cells may play an important immunomodulatory role after allo-HCT.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Friedrich Wittenbecher, Stella Lesch, Stefan Kolling, Igor-Wolfgang Blau, Lam Vuong, Franziska Borchert, Kamran Movasshagi, Carola Tietze-Buerger, Olaf Penack, Johann Ahn, Lars Bullinger, Marco Frentsch, Il-Kang Na
Summary: In this study, a comprehensive phenotypic analysis of 26 immune cell subsets was conducted using multicolor flow cytometry. The analysis was performed on only 100 μL of whole blood samples and provided extensive longitudinal data. The study found that the relative quantitative immune cell subset composition in recipients approached that of healthy donors after 180 days post alloHSCT. The proposed method could be a time efficient approach for broad immune assessment in future clinical studies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Adele Dhuyser, Alice Aarnink, Michael Peres, Jyothi Jayaraman, Neda Nemat-Gorgani, Marie Therese Rubio, John Trowsdale, James Traherne
Summary: Allogeneic hematopoietic stem cell transplantation is a life-saving therapy for hematological malignancies. The selection of a suitable donor has traditionally required a fully matched HLA. However, new immunosuppressive strategies have made it possible to recruit viable alternative donors, including haploidentical donors. The importance of KIR-driven NK cell alloreactivity in aHSCT outcomes remains unclear, and the literature shows discrepancies in the evaluation of its clinical benefit.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Ardiana Moustaki, Jeremy Chase Crawford, Shanta Alli, Yiping Fan, Shannon Boi, Anthony E. Zamora, Natalie M. N. McDonald, Gang Wu, Joy Nakitandwe, Scott Newman, Scott Foy, Antonina Silkov, Paul G. Thomas, Alberto Pappo, Michael A. Dyer, Elizabeth Stewart, Sara Federico, Ben Youngblood
Summary: Age bias affects antitumor immunity, with a young tissue microenvironment leading to an immune response skewed towards a terminal effector state, limiting the window for immunotherapeutic interventions.
SCIENCE IMMUNOLOGY
(2022)
Meeting Abstract
Hematology
Lindsay Hammons, Shabi Haider, Marcelo C. Pasquini, Saurabh Chhabra, Sabarinath Radhakrishnan, Anthony E. Zamora, Meera Mohan, Jing Dong, Siegfried Janz, Anita D'Souza, Parameswaran Hari, Binod Dhakal
Article
Oncology
Claudia Augusta Di Trani, Assunta Cirella, Leire Arrizabalaga, Angela Bella, Myriam Fernandez-Sendin, Joan Salvador Russo-Cabrera, Celia Gomar, Irene Olivera, Elizabeth Bolanos, Jose Gonzalez-Gomariz, Maite Alvarez, Inaki Etxeberria, Belen Palencia, Alvaro Teijeira, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Summary: Previous studies have found that local delivery of tumor antigen-specific CD8(+) T lymphocytes transiently expressing single-chain IL-12 mRNA is highly effective in treating tumors. In this study, intracavitary adoptive T cell therapy was used to treat peritoneal dissemination of B16-OVA and PANC02-OVA tumors, and it was found that intraperitoneal administration of T cells promoted homing to the omentum more effectively than intravenous administration. Transient IL-12 expression resulted in a favorable reprogramming of the tumor immune microenvironment and longer persistence of transferred T lymphocytes, leading to the development of immunity to endogenous antigens after primary tumor eradication.
Article
Oncology
Maria E. Rodriguez-Ruiz, Irantzu Serrano-Mendioroz, Eneko Garate-Soraluze, Paloma Sanchez-Mateos, Celia Barrio-Alonso, Inmaculada Rodriguez Lopez, Victor Diaz Pascual, Leire Arbea Moreno, Maite Alvarez, Miguel F. Sanmamed, Jose Luis Perez-Gracia, Helena Escuin-Ordinas, Marisol Quintero, Ignacio Melero
Summary: This study demonstrates that local BO-112 immunotherapy and focal irradiation can synergistically achieve local tumor control. Furthermore, irradiation plus BO-112 in one of the tumor lesions enhances the therapeutic effects on distant irradiated lesions that were not injected with BO-112.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Maite Alvarez, Carmen Molina, Saray Garasa, Maria C. Ochoa, Maria E. Rodriguez-Ruiz, Gabriel Gomis, Assunta Cirella, Irene Olivera, Javier Glez-Vaz, Jose Gonzalez-Gomariz, Carlos luri-Rey, Arantza Azpilikueta, Elixabet Bolanos, Alvaro Teijeira, Pedro Berraondo, Marisol Quintero, Ignacio Melero
Summary: The poly I:C-based viral mimetic BO-112 has been found to effectively reduce tumor metastasis when intratumorally delivered, particularly when combined with systemic anti-PD-1 mAbs. This neoadjuvant immunotherapy approach relies on antigen-specific effector CD8 T cells and cDC1 antigen-presenting cells.
Article
Cell Biology
Irene Olivera, Elixabet Bolanos, Jose Gonzalez-Gomariz, Sandra Hervas-Stubbs, Karina V. Marino, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Josune Egea, Javier Glez-Vaz, Saray Garasa, Maite Alvarez, Inaki Eguren-Santamaria, Sonia Guedan, Miguel F. Sanmamed, Pedro Berraondo, Gabriel A. Rabinovich, Alvaro Teijeira, Ignacio Melero
Summary: Engineering tumor-specific CD8 T cells with IL-12 mRNA enhances their therapeutic potency when delivered intratumorally.
CELL REPORTS MEDICINE
(2023)
Article
Cell Biology
Maria Carmen Ochoa, Sandra Sanchez-Gregorio, Carlos E. de Andrea, Saray Garasa, Maite Alvarez, Irene Olivera, Javier Glez-Vaz, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Arantza Azpilikueta, Pedro Berraondo, Josepmaria Argemi, Bruno Sangro, Alvaro Teijeira, Ignacio Melero
Summary: Immune checkpoint-inhibitor combinations are the best therapeutic option for advanced hepatocellular carcinoma (HCC) patients, and the efficacy can be further improved by combining recombinant IL-2 or anti-CD137 mAb with anti-CTLA-4 + anti-PD1 mAbs treatment. A multifocal HCC model was developed to test immunotherapies, and the combination of tumor-specific adoptive T cell therapy with aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 regimens showed synergistic efficacy. The combined immunotherapy treatments enhanced T cell infiltration and the intratumoral performance of T lymphocytes.
CELL REPORTS MEDICINE
(2023)
Letter
Biophysics
Mingqian Lin, Noel Estrada-Merly, Mary Eapen, Anthony E. Zamora, Liliana E. Pezzin, Aaron N. Winn, Joyce Philip, Carolina Schinke, William R. Drobyski, Larry D. Anderson, Anita D'Souza
BONE MARROW TRANSPLANTATION
(2023)
Article
Medicine, Research & Experimental
Ignacio Melero, Maria C. Ochoa, Carmen Molina, Sandra Sanchez-Gregorio, Saray Garasa, Carlos Luri-Rey, Sandra Hervas-Stubbs, Noelia Casares, Edurne Elizalde, Gabriel Gomis, Assunta Cirella, Pedro Berraondo, Alvaro Teijeira, Maite Alvarez
Summary: NK cell reactivity against cancer is suppressed in the tumor microenvironment through the interaction of the inhibitory receptor NKG2A with non-classical MHC-I molecules. Injection of anti-NKG2A and anti-Qa-1(b) antibodies enhances the therapeutic effects of NK cells and shows partial efficacy against distant tumors. In experiments with human cancer cells expressing HLA-E, injection of activated allogeneic human NK cells and anti-NKG2A antibodies synergistically achieve therapeutic effects.
EMBO MOLECULAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Assunta Cirella, Elixabet Bolanos, Carlos Luri-Rey, Claudia Augusta Di Trani, Irene Olivera, Gabriel Gomis, Javier Glez-Vaz, Beatrice Pinci, Saray Garasa, Sandra Sanchez-Gregorio, Arantza Azpilikueta, Inaki Eguren-Santamaria, Karmele Valencia, Belen Palencia, Maite Alvarez, Maria C. Ochoa, Alvaro Teijeira, Pedro Berraondo, Ignacio Melero
Summary: Intratumoral immunotherapy strategies for cancer based on IL-12 encoding cDNA and mRNA combined with anti-PD-(L)1 monoclonal antibodies are being developed. Chimeric mRNAs encoding single-chain IL-12 fused to scFv antibodies binding to TGF-b and CD137 have been constructed. Efficacy was observed in mouse cancer models following mRNA intratumoral injections, and distant effects on untreated lesions were increased when combined with systemic PD-1 blockade.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Multidisciplinary Sciences
Javier Glez-Vaz, Arantza Azpilikueta, Maria C. Ochoa, Irene Olivera, Gabriel Gomis, Asunta Cirella, Carlos Luri-Rey, Maite alvarez, Jose. L. L. Perez-Gracia, Sergio Ciordia, Inaki Eguren-Santamaria, Raluca Alexandru, Pedro Berraondo, Carlos de Andrea, Alvaro Teijeira, Fernando Corrales, Juan. M. M. Zapata, Ignacio Melero
Summary: CD137 is a member of the TNFR family that mediates potent T cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies (mAbs). The physical association between cIAP1/cIAP2 and the CD137 signaling complex is demonstrated. cIAPs are required for CD137 signaling towards NF-κB and MAPK pathways, and for the costimulation of human and mouse T lymphocytes.
Article
Oncology
Angela Bella, Leire Arrizabalaga, Claudia Augusta Di Trani, Jose Gonzalez-Gomariz, Celia Gomar, Joan Salvador Russo-Cabrera, Irene Olivera, Assunta Cirella, Myriam Fernandez-Sendin, Maite Alvarez, Alvaro Teijeira, Cigdem Atay, Jose Medina-Echeverz, Maria Hinterberger, Hubertus Hochrein, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Summary: Intraperitoneal administration of MVA vectors encoding scIL-12 can stimulate immune response mediated by tumor-specific CD8+ T lymphocytes and effectively inhibit tumor growth in the peritoneal cavity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Meeting Abstract
Oncology
Allison Kirk, Jeremy Crawford, Ching-Heng Chou, Phuong Nguyen, Walid Awad, E. Kaitlynn Allen, Xiaoyu Zhang, Anthony Zamora, Christopher DeRenzo, Scott Strome, Paul Thomas
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Meeting Abstract
Oncology
Allison M. Kirk, Ching-Heng Chou, Jeremy Chase Crawford, Walid Awad, E. Kaitlynn Allen, Xiaoyu Zhang, Anthony E. Zamora, Scott E. Strome, Paul G. Thomas
Meeting Abstract
Immunology
Allison M. Kirk, Ching-Heng Chou, Walid Awad, Jeremy Chase Crawford, E. Kaitlynn Allen, Xiaoyu Zhang, Anthony E. Zamora, Scott E. Strome, Paul G. Thomas
JOURNAL OF IMMUNOLOGY
(2022)
