Review
Pharmacology & Pharmacy
Pierre Machy, Erwan Mortier, Stephane Birkle
Summary: Ganglioside GD2, a complex glycolipid located on the cell membrane, exhibits diverse expression patterns and functions. Its overexpression in cancer enhances cell survival and invasion, while also contributing to T-cell dysfunction and functioning as an immune checkpoint. These cancer-associated functions make GD2 a potential target for immunotherapy.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Johanna Theruvath, Marie Menard, Benjamin A. H. Smith, Miles H. Linde, Garry L. Coles, Guillermo Nicolas Dalton, Wei Wu, Louise Kiru, Alberto Delaidelli, Elena Sotillo, John L. Silberstein, Anna C. Geraghty, Allison Banuelos, Molly Thomas Radosevich, Shaurya Dhingra, Sabine Heitzeneder, Aidan Tousley, John Lattin, Peng Xu, Jing Huang, Nicole Nasholm, Andy He, Tracy C. Kuo, Emma R. B. Sangalang, Jaume Pons, Amira Barkal, Rachel E. Brewer, Kristopher D. Marjon, Jose G. Vilches-Moure, Payton L. Marshall, Ricardo Fernandes, Michelle Monje, Jennifer R. Cochran, Poul H. Sorensen, Heike E. Daldrup-Link, Irving L. Weissman, Julien Sage, Ravindra Majeti, Carolyn R. Bertozzi, William A. Weiss, Crystal L. Mackall, Robbie G. Majzner
Summary: The combination of anti-GD2 and CD47 blockade demonstrates robust anti-tumor activity in mouse models, particularly effective against neuroblastoma, osteosarcoma, and small-cell lung cancer.
Article
Multidisciplinary Sciences
Babak Moghimi, Sakunthala Muthugounder, Samy Jambon, Rachelle Tibbetts, Long Hung, Hamid Bassiri, Michael D. Hogarty, David M. Barrett, Hiroyuki Shimada, Shahab Asgharzadeh
Summary: The study highlights the importance of developing gated systems for predicting clinical toxicity of CAR T cells in solid tumors. By utilizing murine and human CAR-T cells specific for tumor antigens, the researchers were able to generate a GD2-B7H3 CAR-T with improved metabolic fitness and efficacy in controlling neuroblastoma growth in preclinical models. This innovative approach shows promising results in suppressing neuroblastoma with minimal adverse effects.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Leah Klingel, Nikolai Siebert, Sascha Troschke-Meurer, Maxi Zumpe, Karoline Ehlert, Stefanie Huber, Hans Loibner, Oliver Mutschlechner, Holger N. Lode
Summary: This study investigates the effects of an anti-idiotypic vaccine based on mAb ganglidiomab on HR-NB patients. The results show that the vaccine induces immune responses in most patients without severe side effects.
Article
Oncology
Thomas Blom, Roosmarijn Lurvink, Leonie Aleven, Maarten Mensink, Tom Wolfs, Miranda Dierselhuis, Natasha van Eijkelenburg, Kathelijne Kraal, Max van Noesel, Martine van Grotel, Godelieve Tytgat
Summary: The study described treatment-related toxicities during immunotherapy with dinutuximab, IL-2, GM-CSF, and isotretinoin in high-risk neuroblastoma patients, showing that a significant proportion of patients discontinued immunotherapy due to disease progression, isotretinoin-associated liver toxicity, and catheter-related infection. Common grade >= 3 toxicities included pain, catheter-related infections, and fever.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pediatrics
William S. Panosyan, Daniel E. Panosyan, Jan Koster, Eduard H. Panosyan
Summary: Oncometabolism is a potential target for developing less myelotoxic cancer therapies, and lactate dehydrogenase A (LDHA) is crucial to the Warburg effect in neuroblastoma (NBL). Although advanced surgical, cytotoxic, and cell-differentiating therapies have improved the survival of children with NBL, the clinical outcomes for high-risk NBL still need improvement. This study confirms the prognostic value of LDHA expression in NBL and proposes the development of an immunoliposome loaded with an LDHA inhibitor, Oxamate, for targeted delivery using anti-GD2 monoclonal antibodies (mAb).
PEDIATRIC RESEARCH
(2023)
Review
Oncology
Jaume Mora, Shakeel Modak, Joyce Kinsey, Carolyn E. Ragsdale, Hillard M. Lazarus
Summary: Colony-stimulating factors, such as GM-CSF, have been studied extensively for their potential to enhance the effectiveness of anti-GD2 monoclonal antibodies in high-risk neuroblastoma. However, access to these therapies is not uniform, and there is limited clinical data supporting the use of G-CSF as an alternative to GM-CSF. More research is needed to ensure equitable access to these treatments globally.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Marjolein C. Stip, Mitchell Evers, Maaike Nederend, Chilam Chan, Karli R. Reiding, Mirjam J. Damen, Albert J. R. Heck, Sofia Koustoulidou, Ruud Ramakers, Gerard C. Krijger, Remmert de Roos, Edouard Souteyrand, Annelisa M. Cornel, Miranda P. Dierselhuis, Marco Jansen, Mark de Boer, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen, Friederike Meyer-Wentrup
Summary: Researchers engineered an antibody called IgA3.0 ch14.18, which shows promise as a new therapy for neuroblastoma. The antibody has a longer half-life, increased protein stability, and potent tumor-killing abilities.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Evan Rosenbaum, Rashmi Chugh, Christopher W. Ryan, Mark Agulnik, Mohammed M. Milhem, Suzanne George, Robin L. Jones, Bartosz Chmielowski, Brian A. Van Tine, Hussein Tawbi, Anthony D. Elias, William L. Read, G. Thomas Budd, Li-Xuan Qin, Eve T. Rodler, Joe Hirman, Paul Weiden, Cathryn M. Bennett, Philip O. Livingston, Govind Ragupathi, David Hansen, Sandra P. D'Angelo, William D. Tap, Gary K. Schwartz, Robert G. Maki, Richard D. Carvajal
Summary: This study aimed to control recurrence and improve outcomes in sarcoma patients after metastasectomy by administering a KLH-conjugated ganglioside vaccine and the immunological adjuvant OPT-821. Although vaccination induced a sustained serologic response, no differences were observed between treatment arms in terms of relapse-free survival and overall survival.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Andras Heczey, Xin Xu, Amy N. Courtney, Gengwen Tian, Gabriel A. Barragan, Linjie Guo, Claudia Martinez Amador, Nisha Ghatwai, Purva Rathi, Michael S. Wood, Yanchuan Li, Chunchao Zhang, Thorsten Demberg, Erica J. Di Pierro, Andrew C. Sher, Huimin Zhang, Birju Mehta, Sachin G. Thakkar, Bambi Grilley, Tao Wang, Brian D. Weiss, Antonino Montalbano, Meena Subramaniam, Chenling Xu, Chirag Sachar, Daniel K. Wells, Gianpietro Dotti, Leonid S. Metelitsa
Summary: This study presented updated interim results on the evaluation of GD2-specific CAR-expressing NKT cells co-expressing IL15 in children with NB. The results showed that GD2-CAR.15 NKT cells had anti-tumor activity, which could be enhanced by targeting BTG1.
Article
Oncology
Brian H. Kushner, Shakeel Modak, Kim Kramer, Ellen M. Basu, Fiorella Iglesias-Cardenas, Stephen S. Roberts, Nai-Kong Cheung
Summary: This study reports on the feasibility, safety, and long-term survival of infants with high-risk neuroblastoma treated with anti-G(D2) monoclonal antibodies. The results show that infants with HR-NB can achieve high cure rates, and the toxicity observed with short outpatient infusions is similar to that in other age groups.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Enrico Rango, Fabio Pastorino, Chiara Brignole, Arianna Mancini, Federica Poggialini, Salvatore Di Maria, Claudio Zamperini, Giulia Iovenitti, Anna Lucia Fallacara, Samantha Sabetta, Letizia Clementi, Massimo Valoti, Silvia Schenone, Adriano Angelucci, Mirco Ponzoni, Elena Dreassi, Maurizio Botta
Summary: Si306, an anticancer agent, has shown favorable activity against neuroblastoma models. However, its sub-optimal aqueous solubility poses a limitation for its development. In this study, Si306 was encapsulated into liposomes and modified with an antibody specific for neuroblastoma cells. The modified liposomes demonstrated increased cellular targeting and cytotoxic activity. In animal experiments, Si306 encapsulated in targeted liposomes showed significantly higher tumor uptake and improved survival rates.
Review
Biochemistry & Molecular Biology
Godfrey Chi-Fung Chan, Carol Matias Chan
Summary: Neuroblastoma is a childhood cancer with a specific antigen known as GD2. Monoclonal antibodies targeting GD2 have been used successfully in high-risk cases, but there are variations in the products and administration regimens. The long-term efficacy and challenges related to immune evasion and resistance still need further investigation.
Article
Oncology
Fiorella Iglesias Cardenas, Audrey Mauguen, Irene Y. Cheung, Kim Kramer, Brian H. Kushner, Govind Ragupathi, Nai-Kong V. Cheung, Shakeel Modak
Summary: Beta glucans, along with 3F8, showed anti-neuroblastoma activity with no major toxicity, providing partial or complete response in some treated patients. Positive responses were associated with specific genetic factors and not correlated with beta glucans dose or serum levels.
Article
Oncology
Nathaniel W. Mabe, Min Huang, Guillermo N. Dalton, Gabriela Alexe, Daniel A. Schaefer, Anna C. Geraghty, Amanda L. Robichaud, Amy S. Conway, Delan Khalid, Marius M. Mader, Julia A. Belk, Kenneth N. Ross, Michal Sheffer, Miles H. Linde, Nghi Ly, Winnie Yao, Maria Caterina Rotiroti, Benjamin A. H. Smith, Marius Wernig, Carolyn R. Bertozzi, Michelle Monje, Constantine S. Mitsiades, Ravindra Majeti, Ansuman T. Satpathy, Kimberly Stegmaier, Robbie G. Majzner
Summary: Mabe et al. found that the levels of GD2 are associated with lineage plasticity in neuroblastoma, and they identified ST8SIA1 as the critical enzyme in GD2 synthesis. Inhibition of EZH2 in mesenchymal neuroblastoma cells increases ST8SIA1 expression, synergizing with anti-GD2 antibodies. However, there is a lack of understanding about the mechanisms of resistance to anti-GD2 therapy. This study reveals that reduced GD2 expression is significantly correlated with the mesenchymal cell state in neuroblastoma, and a forced adrenergic-to-mesenchymal transition (AMT) leads to GD2 downregulation and resistance to anti-GD2 antibody. The pharmacologic inhibition of EZH2 results in epigenetic rewiring of mesenchymal neuroblastoma cells, enabling re-expression of ST8SIA1, restoration of GD2 surface expression, and sensitivity to anti-GD2 antibody.
Article
Oncology
Annu Singh, Shakeel Modak, Armand K. Solano, Brian H. Kushner, Suzanne Wolden, Joseph Huryn, Cherry L. Estilo
Summary: This retrospective study reviewed medical records of patients with NB and MM, finding that MM at diagnosis has a similar prognosis to other skeletal metastases of NB. Radiotherapy is effective in controlling MM both at diagnosis and relapse. Dental abnormalities post-therapy require regular evaluations and intervention.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Oncology
Sanam Shahid, Brian H. Kushner, Shakeel Modak, Ellen M. Basu, Elyssa M. Rubin, Gunes Gundem, Elli Papaemmanuil, Stephen S. Roberts
Summary: In rare cases of high-risk neuroblastoma (HR-NB), vasoactive intestinal peptide-related diarrhea (VIP-D) can be effectively treated with BRAF and MEK inhibitors, resolving symptoms associated with BRAF V600E mutations. This therapeutic strategy allows continued conventional tumor-directed treatment in HR-NB patients, reducing the severity of complications caused by VIP-D.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Oncology
Barbara Spitzer, Kayleigh D. Rutherford, Gunes Gundem, Erin M. McGovern, Nathan E. Millard, Juan E. Arango Ossa, Irene Y. Cheung, Teng Gao, Max F. Levine, Yanming Zhang, Juan S. Medina-Martinez, Yi Feng, Ryan N. Ptashkin, Kelly L. Bolton, Noushin Farnoud, Yangyu Zhou, Minal A. Patel, Georgios Asimomitis, Cassidy C. Cobbs, Neeman Mohibullah, Kety H. Huberman, Maria E. Arcilla, Brian H. Kushner, Shakeel Modak, Andrew L. Kung, Ahmet Zehir, Ross L. Levine, Scott A. Armstrong, Nai Kong Cheung, Elli Papaemmanuil
Summary: This study aimed to explore the relationship between the development of t-MDS/AL and molecular abnormalities in pediatric patients with high-risk neuroblastoma. The study found that at least one disease-defining alteration was detected in all cases at t-MDS/AL diagnosis, with TP53 gene mutations and KMT2A gene rearrangements being the most common. Compared to the transient and control groups, t-MDS/AL patients had acquired mutations at an earlier stage before the onset of the disease. Additionally, the study revealed that only a small number of pediatric patients with solid tumors had clonal hematopoiesis involving myeloid genes.
CLINICAL CANCER RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Milan Grkovski, Pat B. Zanzonico, Shakeel Modak, John L. Humm, Jagat Narula, Neeta Pandit-Taskar
Summary: This study aimed to assess the feasibility of using MFBG PET imaging to evaluate myocardial sympathetic innervation. The results showed that MFBG uptake was rapid and sustained, making it a promising tool for quantitatively evaluating myocardial sympathetic innervation. The results were consistent with the heart-to-mediastinum activity concentration ratio obtained from MIBG SPECT.
JOURNAL OF NUCLEAR CARDIOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Milan Grkovski, Shakeel Modak, Pat B. Zanzonico, Jorge A. Carrasquillo, Steven M. Larson, John L. Humm, Neeta Pandit-Taskar
Summary: The study aimed to evaluate the pharmacokinetics, biodistribution, and radiation dosimetry of I-124-omburtamab in patients with desmoplastic small round cell tumor. The results showed heterogeneous and diffuse distribution of the drug in the peritoneal cavity, with low activity in major organs. The absorbed doses in liver, spleen, and kidneys were relatively low, indicating minimal toxicity.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Oncology
Fiorella Iglesias Cardenas, Audrey Mauguen, Irene Y. Cheung, Kim Kramer, Brian H. Kushner, Govind Ragupathi, Nai-Kong V. Cheung, Shakeel Modak
Summary: Beta glucans, along with 3F8, showed anti-neuroblastoma activity with no major toxicity, providing partial or complete response in some treated patients. Positive responses were associated with specific genetic factors and not correlated with beta glucans dose or serum levels.
Article
Multidisciplinary Sciences
N. Shukla, M. F. Levine, G. Gundem, D. Domenico, B. Spitzer, N. Bouvier, J. E. Arango-Ossa, D. Glodzik, J. S. Medina-Martinez, U. Bhanot, J. Gutierrez-Abril, Y. Zhou, E. Fiala, E. Stockfisch, S. Li, M. Rodriguez-Sanchez, T. O'Donohue, C. Cobbs, M. H. A. Roehrl, J. Benhamida, F. Iglesias Cardenas, M. Ortiz, M. Kinnaman, S. Roberts, M. Ladanyi, S. Modak, S. Farouk-Sait, E. Slotkin, M. A. Karajannis, F. Dela Cruz, J. Glade Bender, A. Zehir, A. Viale, M. F. Walsh, A. L. Kung, E. Papaemmanuil
Summary: The authors developed a workflow to deliver comprehensive cWGTS results within clinically-relevant timeframes. Compared to other diagnostic methods, cWGTS has the potential to capture all clinically reported mutations with comparable sensitivity. These findings provide important technical considerations for implementing cWGTS in clinical oncology.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Brian H. Kushner, Shakeel Modak, Kim Kramer, Ellen M. Basu, Fiorella Iglesias-Cardenas, Stephen S. Roberts, Nai-Kong Cheung
Summary: This study reports on the feasibility, safety, and long-term survival of infants with high-risk neuroblastoma treated with anti-G(D2) monoclonal antibodies. The results show that infants with HR-NB can achieve high cure rates, and the toxicity observed with short outpatient infusions is similar to that in other age groups.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Kim Kramer, Neeta Pandit-Taskar, Brian H. Kushner, Pat Zanzonico, John L. Humm, Ursula Tomlinson, Maria Donzelli, Suzanne L. Wolden, Sophia Haque, Ira Dunkel, Mark M. Souweidane, Jeffrey P. Greenfield, Satish Tickoo, Jason S. Lewis, Serge K. Lyashchenko, Jorge A. Carrasquillo, Bae Chu, Christopher Horan, Steven M. Larson, Nai-Kong V. Cheung, Shakeel Modak
Summary: The prognosis for metastatic and recurrent tumors of the central nervous system (CNS) remains dismal. This study explored the use of intraventricular radioimmunotherapy with anti-B7H3 antibody Omburtamab for targeting CNS malignancies. The results showed promising therapeutic benefits and favorable dosimetry and safety.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Kathryn R. Tringale, Suzanne L. Wolden, Dana L. Casey, Brian H. Kushner, Leo Luo, Neeta Pandit-Taskar, Mark Souweidane, Nai-Kong Cheung, Shakeel Modak, Ellen M. Basu, Kim Kramer
Summary: Neuroblastoma patients who experience CNS relapse after CSI have a poor prognosis. Surgery combined with hypofractionated radiotherapy is the most common treatment approach. The use of cRIT, whether in the first or second CNS relapse, is associated with improved survival. Further investigation is needed to explore this finding.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Oncology
Irene Y. Cheung, Audrey Mauguen, Shakeel Modak, Govind Ragupathi, Ellen M. Basu, Stephen S. Roberts, Brian H. Kushner, Nai-Kong Cheung
Summary: This clinical trial investigated the effects of oral beta-glucan adjuvant during vaccine priming in patients with high-risk neuroblastoma. It was found that adding oral beta-glucan increased anti-GD2 IgG1 antibody levels without additional toxic effects. However, alternative adjuvants may be needed to improve seroconversion rates.
Article
Oncology
Christina Fong, Brian H. Kushner, Angela Di Giannatale, Gunes Gundem, Shanita Li, Stephen S. Roberts, Ellen M. Basu, Anita Price, Nai-Kong V. Cheung, Shakeel Modak
Summary: This retrospective study investigated the significance of skeletal muscle metastases (SMM) in neuroblastoma. The findings suggest that children with neuroblastoma SMM have an excellent prognosis, similar to stage MS disease. Therefore, watchful observation could be a suitable initial management approach for infants with non-MYCN-amplified NB with SMM, potentially avoiding unnecessary exposure to genotoxic therapy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Neeta Pandit-Taskar, Milan Grkovski, Pat B. Zanzonico, Keith S. Pentlow, Shakeel Modak, Kim Kramer, John L. Humm
Summary: In this study, the authors used radiolabeled antibody treatment with 131I-omburtamab to deliver therapeutic doses to leptomeningeal disease sites. They assessed the distribution and radiation dosimetry using pretreatment imaging and dosimetric analysis. The results showed effective localization in the ventricles and spinal CSF space with low systemic distribution. The study highlights the importance of pretherapeutic imaging for assessing biodistribution and dosimetry. Overall, this study is rated 8 out of 10 in terms of its importance.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Oncology
Elise M. Fiala, Gowtham Jayakumaran, Audrey Mauguen, Jennifer A. Kennedy, Nancy Bouvier, Yelena Kemel, Megan Harlan Fleischut, Anna Maio, Erin E. Salo-Mullen, Margaret Sheehan, Angela G. Arnold, Alicia Latham, Maria I. Carlo, Karen Cadoo, Semanti Murkherjee, Emily K. Slotkin, Tanya Trippett, Julia Glade Bender, Paul A. Meyers, Leonard Wexler, Filemon S. Dela Cruz, Nai-Kong Cheung, Ellen Basu, Alex Kentsis, Michael Ortiz, Jasmine H. Francis, Ira J. Dunkel, Yasmin Khakoo, Stephen Gilheeney, Sameer Farouk Sait, Christopher J. Forlenza, Maria Sulis, Matthias Karajannis, Shakeel Modak, Justin T. Gerstle, Todd E. Heaton, Stephen Roberts, Ciyu Yang, Sowmya Jairam, Joseph Vijai, Sabine Topka, Danielle N. Friedman, Zsofia K. Stadler, Mark Robson, Michael F. Berger, Nikolaus Schultz, Marc Ladanyi, Richard J. O'Reilly, David H. Abramson, Ozge Ceyhan-Birsoy, Liying Zhang, Diana Mandelker, Neerav N. Shukla, Andrew L. Kung, Kenneth Offit, Ahmet Zehir, Michael F. Walsh
Summary: This study reported the results of prospective DNA sequencing in pediatric solid tumor patients, identifying germline variants associated with high and moderate penetrance genes, some of which were unexpected. Most patients with positive results underwent clinical genetics consultation, and some relatives also underwent cascade testing.
