Review
Immunology
Feifei Li, Sheng Liu
Summary: This review provides an overview of the role of natural killer (NK) cells and antibody-dependent cellular cytotoxicity (ADCC) in targeted therapy of HER2-positive breast cancer, as well as recent strategies to leverage our knowledge of NK cells and ADCC as an immunotherapy approach.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Kate J. Dixon, Jianming Wu, Bruce Walcheck
Summary: Human natural killer (NK) cells target tumor antigens through interaction with IgG Fc receptors, leading to antibody-dependent cell-mediated cytotoxicity (ADCC) against cancer cells. Engineering monoclonal antibodies and Fc receptors can enhance NK cell-mediated ADCC for cancer treatment. Targeting tumor antigens by modifying the Fc portion of antibodies or the FcR on NK cells is a key focus of research in improving mAb therapy efficacy.
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)
Review
Biochemistry & Molecular Biology
Fabiola De Luca, Alessandro Allegra, Carla Di Chio, Santo Previti, Maria Zappala, Roberta Ettari
Summary: Multiple myeloma is an incurable hematologic cancer characterized by immunological alterations in myeloid cells and lymphocytes. The current first-line therapy involves chemotherapy, but there is a high relapse rate and refractory MM cases. New monoclonal antibodies (Mab) including daratumumab, isatuximab, and elotuzumab, along with bispecific antibodies and CAR T cell therapy, have shown promise in immunotherapy for MM. CD38 (daratumumab and isatuximab), SLAM7 (elotuzumab) and BCMA (belantamab mafodotin) are the main antibody targets for MM treatment. Although MM is still incurable, combining the available drugs offers hope for improving outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Lois Coenon, Martin Villalba
Summary: This review provides an overview of the latest strategies employed to improve antibody-dependent NK cell cytotoxicity, by enhancing the biological function of CD16a receptor.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Massimo Fantini, Philip Martin Arlen, Kwong Yok Tsang
Summary: Natural killer (NK) cells are important components of the innate immune system that can recognize and suppress the proliferation of cancer cells. Strategies such as boosting NK cells with modulatory cytokines, adoptive NK cell therapy, and the combination of engineered NK cells with monoclonal antibodies (mAbs) that mediate antibody-dependent cell-mediated cytotoxicity (ADCC) have been developed to enhance the antitumor activity of NK cells. The combination of engineered NK cells with mAbs with higher affinity for CD16 expressed on NK cells shows promise in providing more effective and higher-quality treatments for cancer patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Federico Vozella, Francesca Fazio, Gianfranco Lapietra, Maria T. Petrucci, Giovanni Martinelli, Claudio Cerchione
Summary: In recent years, the treatment landscape for multiple myeloma patients has seen significant advancements with the introduction of next-generation proteasome inhibitors, immunomodulatory derivatives, and monoclonal antibodies. Monoclonal antibodies offer a promising new approach with immune-based mechanisms that induce durable responses and have shown effectiveness in heavily pretreated or double refractory patients. These antibodies work through various pathways, including ADCC, ADCP, CDC, and the induction of signals on cell effectors, targeting key molecular pathways involved in the survival of malignant plasma cells.
Article
Immunology
Antonio Hrvat, Mathias Schmidt, Martin Obholzer, Sonja Benders, Sebastian Kollenda, Peter A. Horn, Matthias Epple, Sven Brandau, Nina Mallmann-Gottschalk
Summary: The study explores the effects of different CaP-NPs on the anti-tumor activity of natural killer (NK) cells. Aggregated CaP-NPs can activate NK cell degranulation and impair antibody-dependent cellular cytotoxicity (ADCC). However, when properly dissolved, they do not cause substantial activation. Functionalized CaP-NPs coupled with therapeutic antibodies maintain high levels of ADCC activity.
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)
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)
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
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.
Review
Oncology
Meera Mohan, Theresa Camille Maatman, Carolina Schinke
Summary: The introduction of monoclonal antibodies in the treatment of multiple myeloma has significantly improved patient outcomes, but the majority of patients will eventually relapse, highlighting the need for novel therapies like bispecific antibodies and chimeric antigen receptor T cells. These emerging treatments show promising results in heavily pretreated and refractory patients, and there is optimism that they may lead to sustained remission and a possible cure in the future.
Review
Oncology
Aurelia Chacon, Xavier Leleu, Arthur Bobin
Summary: The treatment of multiple myeloma (MM) has drastically improved over the years, especially for elderly patients. Chemotherapy was the main treatment for MM in the past, but targeted therapies such as immunomodulating agents and proteasome inhibitors have led to increased survival rates. The introduction of monoclonal antibodies has been a significant advancement in MM treatment for both transplant-eligible and non-transplant-eligible patients. However, further progress is expected with the use of innovative immunotherapy-based treatments like CAR-T cells and bispecific antibodies.
Review
Cell Biology
Alireza Isazadeh, Saba Hajazimian, Hamid Garshasbi, Behrouz Shadman, Amir Baghbanzadeh, Reza Chavoshi, Sina Taefehshokr, Mahdieh Farhoudi Sefidan Jadid, Khalil Hajiasgharzadeh, Behzad Baradaran
Summary: Multiple myeloma is characterized by neoplastic proliferation of plasma cells in the bone marrow. Immune checkpoint inhibitors show anticancer activity in various solid and liquid cancers, but limited efficacy due to resistance is a common challenge for patients.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Oncology
Adam D. Cohen, Noopur Raje, Jessica A. Fowler, Khalid Mezzi, Emma C. Scott, Madhav V. Dhodapkar
CLINICAL CANCER RESEARCH
(2020)
Article
Oncology
Sikander Ailawadhi, Rachael Sexton, Suzanne Lentzsch, Muneer H. Abidi, Peter M. Voorhees, Adam D. Cohen, Eric M. Rohren, Stephen Heitner, Kevin Kelly, Niklas J. Mackler, David M. Baer, Antje Hoering, Brian Durie, Robert Z. Orlowski
CLINICAL CANCER RESEARCH
(2020)
Article
Oncology
Paul G. Richardson, Hans C. Lee, Al-Ola Abdallah, Adam D. Cohen, Prashant Kapoor, Peter M. Voorhees, Axel Hoos, Karrie Wang, January Baron, Trisha Piontek, Julie Byrne, Scott Richmond, Roxanne C. Jewell, Joanna Opalinska, Ira Gupta, Sagar Lonial
BLOOD CANCER JOURNAL
(2020)
Article
Oncology
Shwetha H. Manjunath, Adam D. Cohen, Simon F. Lacey, Megan M. Davis, Alfred L. Garfall, J. Joseph Melenhorst, Russell Maxwell, W. Tristram Arscott, Amit Maity, Joshua A. Jones, John P. Plastaras, Edward A. Stadtmauer, Bruce L. Levine, Carl H. June, Michael C. Milone, Ima Paydar
Summary: This study evaluated the safety and feasibility of bridging radiation in CART-BCMA therapy for r/rMM patients. Results showed that bridging radiation may decrease certain grades of toxicities, but larger studies are needed for definitive conclusions.
CLINICAL CANCER RESEARCH
(2021)
Letter
Oncology
Alfred Garfall, Adam Cohen, Edward Stadtmauer, Sandra Susanibar-Adaniya, Dan Vogl, Adam Waxman
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Daniel Hirschhorn, Allison Betof Warner, Rachana Maniyar, Andrew Chow, Levi Mb Mangarin, Adam D. Cohen, Linda Hamadene, Gabrielle A. Rizzuto, Sadna Budhu, Nathan Suek, Cailian Liu, Alan N. Houghton, Taha Merghoub, Jedd D. Wolchok
Summary: The combination therapy of cyclophosphamide (CTX) and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonism controlled tumor growth in clinically relevant mouse models by causing tumor cell death, clonal expansion of highly active CD8+ T cells, and depletion of Tregs. This rational chemoimmunotherapeutic approach led to an expanded population of highly activated, tumor-infiltrating, oligoclonal CD8+ T cells that resulted in a diminished TCR repertoire. The efficacy of this combination therapy warrants further clinical investigation.
Article
Oncology
Sandra Susanibar Adaniya, Edward A. Stadtmauer, Adam D. Cohen
Article
Oncology
Adam D. Cohen, Samir Parekh, Bianca D. Santomasso, Jaime Gallego Perez-Larraya, Niels W. C. J. van de Donk, Bertrand Arnulf, Maria-Victoria Mateos, Nikoletta Lendvai, Carolyn C. Jackson, Kevin C. De Braganca, Jordan M. Schecter, Loreta Marquez, Erin Lee, Ingrid Cornax, Enrique Zudaire, Claire Li, Yunsi Olyslager, Deepu Madduri, Helen Varsos, Lida Pacaud, Muhammad Akram, Dong Geng, Andrzej Jakubowiak, Hermann Einsele, Sundar Jagannath
Summary: This study assessed the associated factors for movement and neurocognitive treatment-emergent adverse events (MNTs) in patients with multiple myeloma treated with cilta-cel. Strategies were implemented to monitor and manage patients with MNTs, leading to a significant reduction in the incidence of adverse events.
BLOOD CANCER JOURNAL
(2022)
Article
Oncology
Thomas Martin, Saad Z. Usmani, Jesus G. Berdeja, Mounzer Agha, Adam D. Cohen, Parameswaran Hari, David Avigan, Abhinav Deol, Myo Htut, Alexander Lesokhin, Nikhil C. Munshi, Elizabeth O'Donnell, A. Keith Stewart, Jordan M. Schecter, Jenna D. Goldberg, Carolyn C. Jackson, Tzu-Min Yeh, Arnob Banerjee, Alicia Allred, Enrique Zudaire, William Deraedt, Yunsi Olyslager, Changwei Zhou, Lida Pacaud, Deepu Madduri, Andrzej Jakubowiak, Yi Lin, Sundar Jagannath
Summary: PURPOSECARTITUDE-1, a phase Ib/II study, evaluated the safety and efficacy of Ciltacabtagene Autoleucel in heavily treated patients with relapsed/refractory multiple myeloma. The study showed early, deep, and durable responses at 12 months, with updated results at 2 years. Patients received a single infusion of Ciltacabtagene Autoleucel and responses were assessed.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Adam D. Cohen, Maria-Victoria Mateos, Yael C. Cohen, Paula Rodriguez-Otero, Bruno Paiva, Niels W. C. J. van de Donk, Thomas Martin, Attaya Suvannasankha, Kevin C. De Braganca, Christina Corsale, Jordan M. Schecter, Helen Varsos, William Deraedt, Liwei Wang, Martin Vogel, Tito Roccia, Xiaoying Xu, Pankaj Mistry, Enrique Zudaire, Muhammad Akram, Tonia Nesheiwat, Lida Pacaud, Irit Avivi, Jesus San-Miguel
Summary: The CARTITUDE-2 study evaluated the safety and efficacy of cilta-cel in patients with multiple myeloma who had previously received anti-BCMA treatment. The results showed that cilta-cel induced favorable responses in patients who had exhausted other therapies.
Article
Oncology
Adam D. Cohen, Parameswaran Hari, Myo Htut, Jesus G. Berdeja, Saad Z. Usmani, Deepu Madduri, Yunsi Olyslager, Jenna D. Goldberg, Jordan M. Schecter, Carolyn C. Jackson, Katharine S. Gries, John M. Fastenau, Satish Valluri, William Deraedt, Muhammad Akram, Rebecca Crawford, Ross Morrison, Lynda Doward, Kate Morgan, Silene ten Seldam, Andrzej Jakubowiak, Sundar Jagannath
Summary: Ciltacabtagene autoleucel (cilta-cel) is a CAR-T cell therapy that has shown efficacy in patients with relapsed/refractory multiple myeloma and improvements in health-related quality of life. Patient perspectives on cilta-cel treatment provide additional context to clinical outcomes and the majority of patients reported that their expectations were met or exceeded.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Hematology
Morie A. Gertz, Adam D. Cohen, Raymond L. Comenzo, Efstathios Kastritis, Heather J. Landau, Edward N. Libby, Michaela Liedtke, Vaishali Sanchorawala, Stefan Schoenland, Ashutosh Wechalekar, Jeffrey A. Zonder, Giovanni Palladini, Jackie Walling, Spencer Guthrie, Christie Nie, Carol Karp, Yuying Jin, Gene G. Kinney, Giampaolo Merlini
Summary: The VITAL trial assessed the efficacy and safety of birtamimab in combination with standard of care in AL amyloidosis patients. Although no significant difference was observed in the overall results, a post hoc analysis showed significant improvement in survival time at month 9 for Mayo stage IV patients treated with birtamimab.
Article
Oncology
Myo Htut, Binod Dhakal, Adam D. Cohen, Thomas Martin, Jesus G. Berdeja, Saad Z. Usmani, Mounzer Agha, Carolyn C. Jackson, Deepu Madduri, William Deraedt, Enrique Zudaire, Tzu-min Yeh, Xiaoying Xu, Lida Pacaud, Muhammad Akram, Sundar Jagannath
Summary: This study retrospectively analyzed the efficacy and safety of cilta-cel in patients who had received alloSCT prior to treatment. The results showed that cilta-cel had comparable efficacy and safety profiles in patients with and without prior alloSCT.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Oncology
Alfred L. Garfall, Adam D. Cohen, Sandra P. Susanibar-Adaniya, Wei-Ting Hwang, Dan T. Vogl, Adam J. Waxman, Simon F. Lacey, Vanessa E. Gonzalez, Joseph A. Fraietta, Minnal Gupta, Irina Kulikovskaya, Lifeng Tian, Fang Chen, Natalka Koterba, Robert L. Bartoszek, Margaret Patchin, Rong Xu, Gabriela Plesa, Don L. Siegel, Andrea Brennan, Anne Marie Nelson, Regina Ferthio, Angela Cosey, Kim-Marie Shea, Rachel Leskowitz, Megan Four, Wesley Wilson, Fei Miao, Eric Lancaster, Beatriz M. Carreno, Gerald P. Linette, Elizabeth O. Hexner, Regina M. Young, Dexiu Bu, Keith G. Mansfield, Jennifer L. Brogdon, Carl H. June, Michael C. Milone, Edward A. Stadtmauer
Summary: This study conducted a clinical trial of CAR T cells in multiple myeloma patients and found that it can be a safe and effective treatment for the disease. The results demonstrate the relationship between early treatment and CAR T cell reexpansion and durable clinical response.
BLOOD CANCER DISCOVERY
(2023)
Article
Oncology
Kavita M. Dhodapkar, Adam D. Cohen, Akhilesh Kaushal, Alfred L. Garfall, Renee Julia Manalo, Allison R. Carr, Samuel S. McCachren III, Edward A. Stadtmauer, Simon F. Lacey, J. Joseph Melenhorst, Carl H. June, Michael C. Milone, Madhav Dhodapkar
Summary: This study combined multiple approaches to study the tumor/immune cells in the tumor microenvironment of myeloma patients before and after BCMA CAR T therapy. The findings suggest that lower diversity of T-cell receptor repertoire, presence of hyperexpanded clones and exhausted phenotype, as well as the presence of specific cells in the bone marrow are associated with shorter progression-free survival following therapy. Conversely, longer progression-free survival is associated with an increased proportion of certain cells and the emergence of cells expressing marrow-residence genes. Tumor recurrence is associated with the emergence of new dominant clones.
BLOOD CANCER DISCOVERY
(2022)
