Article
Oncology
Margaux Lejeune, Elodie Duray, Matthias Peipp, Beatrice Clemenceau, Frederic Baron, Yves Beguin, Jo Caers
Summary: The study emphasizes the importance of a balanced CD38 expression on target and effector cells, as attempts to alter this balance will affect the susceptibility of multiple myeloma cells towards daratumumab-mediated antibody-dependent cellular cytotoxicity.
Article
Biochemistry & Molecular Biology
Ayano Nakamura, Susumu Suzuki, Jo Kanasugi, Masayuki Ejiri, Ichiro Hanamura, Ryuzo Ueda, Masao Seto, Akiyoshi Takami
Summary: The prognosis of multiple myeloma has drastically improved with the development of new drugs. However, some patients still show resistance to existing therapies, requiring new treatment alternatives. The combination of venetoclax and daratumumab may be particularly effective in certain MM patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Hyunsoo Cho, Kyung Hwan Kim, Hoyoung Lee, Chang Gon Kim, Haerim Chung, Yoon Seok Choi, Su-Hyung Park, June-Won Cheong, Yoo Hong Min, Eui-Cheol Shin, Jin Seok Kim
Summary: By studying NK cells in patients with multiple myeloma, it was found that adaptive NK cells have lower levels of CD38 expression compared to conventional NK cells, and exhibit stronger anti-tumor activity in daratumumab-mediated effector functions. The composition of adaptive NK cells in the bone marrow of patients with multiple myeloma determines their ex vivo functional activity in response to daratumumab.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Femke A. I. Ehlers, Niken M. Mahaweni, Annet van de Waterweg Berends, Thara Saya, Gerard M. J. Bos, Lotte Wieten
Summary: Multiple myeloma (MM) is an incurable disease characterized by malignant plasma cells in the bone marrow. The tumor microenvironment (TME) plays a crucial role in MM growth and is composed of various tumor-associated cells (TAC) that promote immunosuppression. This study explores the interaction between natural killer (NK) cells and TAC, namely tumor-associated macrophages (TAMs) and M1 macrophages, and investigates the potential enhancement of NK cell anti-tumor functions through an ADCC-triggering antibody targeting macrophages.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Medicine, General & Internal
Pieter Sonneveld, Meletios A. Dimopoulos, Mario Boccadoro, Hang Quach, P. Joy Ho, Meral Beksac, Cyrille Hulin, Elisabetta Antonioli, Xavier Leleu, Silvia Mangiacavalli, Aurore Perrot, Michele Cavo, Angelo Belotti, Annemiek Broijl, Francesca Gay, Roberto Mina, Inger S. Nijhof, Niels W. C. J. van de Donk, Eirini Katodritou, Fredrik Schjesvold, Anna Sureda Balari, Laura Rosinol, Michel Delforge, Wilfried Roeloffzen, Tobias Silzle, Annette Vangsted, Hermann Einsele, Andrew Spencer, Roman Hajek, Artur Jurczyszyn, Sarah Lonergan, Tahamtan Ahmadi, Yanfang Liu, Jianping Wang, Diego Vieyra, Emilie M. J. van Brummelen, Veronique Vanquickelberghe, Anna Sitthi-Amorn, Carla J. de Boer, Robin Carson, Paula Rodriguez-Otero, Joan Blade, Philippe Moreau
Summary: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy showed significant improvement in progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Chantal Reina-Ortiz, Michael Constantinides, Alexis Fayd-Herbe-de-Maudave, Jessy Presumey, Javier Hernandez, Guillaume Cartron, Rosana Diez, Isabel Izquierdo, Gemma Azaceta, Luis Palomera, Isabel Marzo, Javier Naval, Alberto Anel, Martin Villalba, David Giraldosa
Summary: The study evaluated the potential of expanded NK cells from two sources combined with mAbs to target primary multiple myeloma cells. Results indicate that umbilical cord blood eNKs are highly cytotoxic against MM cells, while peripheral blood eNKs have significant cytotoxic advantage when combined with daratumumab.
Article
Oncology
Fei Gao, Mauricio Campos Mora, Michael Constantinides, Lois Coenon, Caroline Multrier, Loic Vaillant, Tianxiang Zhang, Martin Villalba
Summary: This study found significant phenotypical and functional differences between g-NK cells in umbilical cord blood and peripheral blood. Unlike g-NK cells in peripheral blood, g-NK cells in umbilical cord blood do not show heightened cytokine production upon CD16 engagement. However, they exhibit elevated levels of IFN-gamma production after in vitro activation, particularly when co-cultured with human cytomegalovirus and plasma from g-NK positive adults.
Article
Oncology
Alejandra Leivas, Ruth M. Risueno, Alma Guzman, Laura Sanchez-Vega, Manuel Perez, Diego Megias, Lucia Fernandez, Rafael Alonso, Antonio Perez-Martinez, Inmaculada Rapado, Joaquin Martinez-Lopez
Summary: This study suggests that side population cells may represent the stem cell compartment in multiple myeloma, and NK cells have anti-myeloma activity against clonogenic stem cells, potentially leading to new treatment strategies.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Letter
Oncology
Quan Ren, Yingling Zu, Hongchang Su, Qiumei Lu, Bin Xiang, Yanping Luo, Jishuai Zhang, Yongping Song
Summary: Researchers synthesized four single VHH-directed anti-BCMA CAR-NK cells and improved their cytotoxicity by altering intracellular and hinge regions, as well as ectopically expressing IL-15. In vitro and in vivo experiments demonstrated that BCMA-CD28-IL15 CAR-NK cells exhibited strong killing ability and cytokine secretion against BCMA+ tumor cells, indicating their potential application in multiple myeloma treatment.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
Review
Immunology
Ondrej Venglar, Julio Rodriguez Bago, Benjamin Motais, Roman Hajek, Tomas Jelinek
Summary: NK cells are a subset of lymphocytes that have cytotoxic and suppressor activity against virus-infected cells and cancer cells. They have potential in targeted immunotherapy for solid and hematological malignancies, including multiple myeloma. However, NK cells are impaired by various cancer defense mechanisms, leading to deficiencies in maturation, chemotaxis, target recognition, and killing.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Hao-Tian Wu, Xiang-Yu Zhao
Summary: CD38 monoclonal antibodies are an effective therapy for multiple myeloma, but they have side effects on antitumoral NK cells. Further evaluation of the NK-mediated immune response is needed to minimize the adverse effects, and combination therapies can enhance the therapeutic efficacy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
Kristine A. Frerichs, Christie P. M. Verkleij, Meletios A. Dimopoulos, Jhon A. Marin Soto, Sonja Zweegman, Mary H. Young, Kathryn J. Newhall, Tuna Mutis, Niels W. C. J. van de Donk
Summary: Daratumumab, a CD38-targeting antibody, shows significant activity in multiple myeloma but resistance often develops. The addition of the PD-L1 checkpoint inhibitor durvalumab at the time of daratumumab failure did not reverse daratumumab-resistance. This suggests that PD-L1 co-targeting may not be sufficient to overcome daratumumab-resistance.
Article
Immunology
Soon Kyu Lee, Pil Soo Sung, Sung-Soo Park, Chang-Ki Min, Heechul Nam, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon
Summary: Among multiple myeloma patients who are HBsAg-negative and receiving daratumumab treatment, there is a significant risk of reactivation of resolved HBV.
CLINICAL INFECTIOUS DISEASES
(2021)
Review
Hematology
Kiran Ejaz, John D. Roback, Sean R. Stowell, Harold C. Sullivan
Summary: Daratumumab is a human monoclonal antibody targeting CD38 expressing-plasma cells, approved for the treatment of multiple myeloma and being investigated for other hematologic malignancies. It has potential applications in treating various antibody-mediated disorders beyond its current approved uses.
TRANSFUSION MEDICINE REVIEWS
(2021)
Article
Hematology
Federico Vozella, A. Siniscalchi, M. Rizzo, T. Za, G. Antolino, U. Coppetelli, A. Piciocchi, A. Andriani, O. Annibali, L. De Rosa, G. Cimino, G. La Verde, V. De Stefano, M. Cantonetti, T. Caravita di Toritto, M. T. Petrucci
Summary: The study aimed to determine the efficacy and toxicity profile of daratumumab in real-world patients with relapsed/refractory multiple myeloma, showing that daratumumab monotherapy is an effective treatment with a favorable safety profile for heavily pre-treated and refractory patients.
ANNALS OF HEMATOLOGY
(2021)
Review
Oncology
D. Araujo, A. Greystoke, S. Bates, A. Bayle, E. Calvo, L. Castelo-Branco, J. de Bono, A. Drilon, E. Garralda, P. Ivy, O. Kholmanskikh, I. Melero, G. Pentheroudakis, J. Petrie, R. Plummer, S. Ponce, S. Postel-Vinay, L. Siu, A. Spreafico, A. Stathis, N. Steeghs, C. Yap, T. A. Yap, M. Ratain, L. Seymour
Summary: In 2021, the FDA Oncology Center of Excellence launched Project Optimus to optimize dosage for oncology drugs. The MDICT Taskforce reviewed and discussed dosage optimization for oncology trials, providing recommendations for trial design and a practical guide for phase I trials. The aim is to improve dosage selection in early clinical trials of new anticancer treatments and ultimately enhance patient outcomes.
ANNALS OF ONCOLOGY
(2023)
Review
Oncology
Ignacio Melero, Miguel F. Sanmamed, Javier Glez-Vaz, Carlos Luri-Rey, Jun Wang, Lieping Chen
Summary: Twenty-five years ago, it was discovered that agonist anti-CD137 monoclonal antibodies enhanced CD8+ T-cell antitumor immunity and effectively eradicated transplanted mouse tumors. Despite causing severe liver inflammation in some patients, the agonist antibody urelumab showed evidence of activity against melanoma and non-Hodgkin lymphoma. CD137's signaling domain has been incorporated into chimeric antigen receptors, improving their efficacy. New CD137 agonists, primarily based on bispecific constructs, are currently being tested in early-phase trials and are showing promising safety and clinical activity.
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
Health Care Sciences & Services
Daniel Jimenez-Sanchez, Alvaro Lopez-Janeiro, Maria Villalba-Esparza, Mikel Ariz, Ece Kadioglu, Ivan Masetto, Virginie Goubert, Maria D. Lozano, Ignacio Melero, David Hardisson, Carlos Ortiz-de-Solorzano, Carlos E. de Andrea
Summary: We present NaroNet, a weakly-supervised deep learning framework that can predict recurrence in low-grade, early-stage endometrial cancer by learning the complex tumor-immune interrelations. Our model achieved high accuracy in assessing the risk of recurrence, outperforming current prognostic factors.
NPJ DIGITAL 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)
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
Georgia M. Beasley, Ari M. VanderWalde, Tawnya L. Bowles, Joseph J. Sacco, Jiaxin Niu, Katy K. Tsai, Jason A. Chesney, Bartosz Chmielowski, Adel Samson, Terence Duane Rhodes, Gino K. In, Anna C. Pavlick, Trisha M. Wise-Draper, Miguel F. Sanmamed, Jeannie Hou, Mark R. Middleton, Kevin Harrington, Celeste Lebbe, Judith Michels, Mohammed M. Milhem
ANNALS OF SURGICAL ONCOLOGY
(2023)
Meeting Abstract
Oncology
Eneko Garate-Soraluze, Irantzu Serrano-Mendioroz, Carlos E. de Andrea, Toni Rullan, Christina Claus, Pablo Umana, Christian klein, Ignacio Melero, Maria E. Rodriguez-Ruiz
Meeting Abstract
Oncology
Javier Glez-Vaz, Arantza Azpilikueta, Maria Carmen Ochoa, Irene Olivera, Gabriel Gomis, Asunta Cirella, Carlos Luri-Rey, Maite Alvarez, Sergio Ciordia, Pedro Berraondo, Alvaro Teijeira, Fernando Corrales, Juan M. Zapata, Ignacio Melero
Meeting Abstract
Oncology
Angela Bella, Leire Arrizabalaga, Claudia Augusta Di Trani, Jose Gonzalez-Gomariz, Assunta Cirella, Irene Olivera, Maite Alvarez, Alvaro Teijeira, Cigdem Atay Langbein, Jose Medina-Echeverz, Maria Hinterberger, Hubertus Hochrein, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Meeting Abstract
Oncology
Oliver Bechter, Carmen Loquai, Stephane Champiat, Jean Francois Baurain, Jean-Jacques Grob, Jochen Utikal, Sylvie Rottey, Alfonso Berrocal, Jessica Hassel, Ana Arance, Miguel F. Sanmamed, Marye Boers-Sonderen, Brian Gastman, Christoffer Gebhardt, Brant Delafontaine, Ugur Sahin, Ozlem Tureci, Giovanni Abbadessa, Gianfranco Di Genova, Patrick Brueck, Rahul Marpadga, Helen Lee, Celeste Lebbe
Meeting Abstract
Oncology
Maite Alvarez, Maria C. Ochoa, Carmen Molina, Alvaro Teijeira, Saray Garasa, Sandra Sanchez-Gregorio, Irene Olivera, Javier Glez-Vaz, Asunta Cirella, Gabriel Gomis, Jose Gonzalez-Gomariz, Pedro Berraondo, Ignacio Melero
Article
Hematology
Bruno Paiva, Irene Manrique, Meletios A. Dimopoulos, Francesca Gay, Chang-Ki Min, Sonja Zweegman, Raphael Teipel, Maria -Victoria Mateos, Nicola Giuliani, Michele Cavo, Christine Rojas Hopkins, Weijun Fu, Kaveri Suryanarayan, Alexander Vorog, Cong Li, Bingxia Wang, Jose Estevam, Richard Labotka, Ajeeta B. Dash, Ivan Spicka
Summary: Measurable residual disease (MRD) evaluation is helpful in determining treatment duration in multiple myeloma (MM). However, limited longitudinal data exists on MRD during maintenance. This study investigated the prognostic value of MRD dynamics and found that MRD status at randomization and MRD dynamics during maintenance impact progression-free survival (PFS) risk. These findings support the significance of MRD assessment during maintenance in MM.