Blood Cancer Discovery最新文献

Dynamics of Immune Reconstitution and Impact on Outcomes Across CAR-T Cell Products in Large B-Cell Lymphoma. 大 B 细胞淋巴瘤 CAR-T 细胞产品的免疫重建动态及其对疗效的影响

IF 11.5

Blood Cancer Discovery Pub Date : 2024-12-12 DOI: 10.1158/2643-3230.BCD-24-0163

Danny Luan, Susan DeWolf, Teng Fei, Sandeep Raj, Gunjan L Shah, Caleb A Lareau, Mohammad Alhomoud, Gilles Salles, Alfredo Rivas-Delgado, Kai Rejeski, Jae H Park, Efrat Luttwak, Alejandro Luna de Abia, Magdalena Corona, Evangelos Ntrivalas, Giulio Cassanello, Marina Gomez-Llobell, Allison Parascondola, Michael Scordo, Katharine C Hsu, M Lia Palomba, Miguel-Angel Perales, Roni Shouval

{"title":"Dynamics of Immune Reconstitution and Impact on Outcomes Across CAR-T Cell Products in Large B-Cell Lymphoma.","authors":"Danny Luan, Susan DeWolf, Teng Fei, Sandeep Raj, Gunjan L Shah, Caleb A Lareau, Mohammad Alhomoud, Gilles Salles, Alfredo Rivas-Delgado, Kai Rejeski, Jae H Park, Efrat Luttwak, Alejandro Luna de Abia, Magdalena Corona, Evangelos Ntrivalas, Giulio Cassanello, Marina Gomez-Llobell, Allison Parascondola, Michael Scordo, Katharine C Hsu, M Lia Palomba, Miguel-Angel Perales, Roni Shouval","doi":"10.1158/2643-3230.BCD-24-0163","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-24-0163","url":null,"abstract":"Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy are subject to profound immune suppression. Dynamics of immune reconstitution (IR) and impacts of IR on outcomes following infusion across CAR-T products are not well understood. Here, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44.9%, lisocabtagene maraleucel 30.4%, tisagenlecleucel 24.7%). Following infusion, patients remain persistently immunosuppressed, with 48.1% having CD4+ T cell counts <200/µL and median CD3-19+ B cell counts remaining zero through 1 year after CAR-T. IR differences exist by product, with fastest CD4+ T cell recovery seen for tisagenlecleucel, driven primarily by more rapid recovery of the CD4+CCR7-45RA- effector memory subset. Natural killer cell, but not CD4+ T cell, recovery is significantly associated with favorable progression-free (HR: 0.647; 95% CI: 0.476-0.880) and overall survival (HR: 0.637; 95% CI: 0.441-0.920) and inversely correlated with inflammatory markers measured at time of infusion.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The crossroads of clonal evolution, differentiation hierarchy and ontogeny in leukemia development.

IF 11.5

Blood Cancer Discovery Pub Date : 2024-12-09 DOI: 10.1158/2643-3230.BCD-24-0235

Christopher M Sturgeon, Elvin Wagenblast, Franco Izzo, Eirini P Papapetrou

引用次数: 0

Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap.

IF 11.5

Blood Cancer Discovery Pub Date : 2024-12-04 DOI: 10.1158/2643-3230.BCD-24-0292

Ola Landgren, Sean M Devlin

引用次数: 0

CD33-CD123 IF-THEN gating reduces toxicity while enhancing the specificity and memory phenotype of AML-targeting CAR-T cells.

IF 11.5

Blood Cancer Discovery Pub Date : 2024-12-03 DOI: 10.1158/2643-3230.BCD-23-0258

Samy Jambon, Jianping Sun, Shawn Barman, Sakunthala Muthugounder, Xue Rachel Bito, Armita Shadfar, Alexandra E Kovach, Brent L Wood, Varsha Thoppey Manoharan, A Sorana Morrissy, Deepa Bhojwani, Alan S Wayne, Michael A Pulsipher, Yong-Mi Kim, Shahab Asgharzadeh, Chintan Parekh, Babak Moghimi

{"title":"CD33-CD123 IF-THEN gating reduces toxicity while enhancing the specificity and memory phenotype of AML-targeting CAR-T cells.","authors":"Samy Jambon, Jianping Sun, Shawn Barman, Sakunthala Muthugounder, Xue Rachel Bito, Armita Shadfar, Alexandra E Kovach, Brent L Wood, Varsha Thoppey Manoharan, A Sorana Morrissy, Deepa Bhojwani, Alan S Wayne, Michael A Pulsipher, Yong-Mi Kim, Shahab Asgharzadeh, Chintan Parekh, Babak Moghimi","doi":"10.1158/2643-3230.BCD-23-0258","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-23-0258","url":null,"abstract":"CAR T-cell therapy has remarkably succeeded in treating lymphoblastic leukemia. However, its success in AML remains elusive due to the risk of on-target off-tumor toxicity to hematopoietic stem and progenitor cells (HSPC) and insufficient T-cell persistence and longevity. Using a SynNotch circuit, we generated a high-precision \"IF-THEN\" gated logical circuit against the combination of CD33 and CD123 AML antigens and demonstrated anti-tumor efficacy against AML cell lines and patient-derived xenografts. Unlike constitutively expressed CD123 CAR-T cells, those expressed through the CD33 SynNotch circuit could preserve HSPCs and lower the risk of on-target off-tumor hematopoietic toxicity. These gated CAR-T cells exhibited lower expression of exhaustion markers (PD1, Tim3, LAG3, and CD39), higher frequency of memory T cells (CD62L+CD45RA+), and enhanced expansion. While targeting AML, the moderated circuit CAR signal also helped to mitigate cytokine release syndrome, potentially addressing one of the ongoing challenges in CAR-T immunotherapy.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New Approvals Advancing Blood Cancer Medicine. 新批准推动血癌医学发展。

IF 11.5

Blood Cancer Discovery Pub Date : 2024-11-27 DOI: 10.1158/2643-3230.BCD-24-0300

引用次数: 0

Total (Immuno)Therapy: Version 2.0. 全面（免疫）疗法》：2.0 版。

IF 11.5

Blood Cancer Discovery Pub Date : 2024-11-26 DOI: 10.1158/2643-3230.BCD-24-0236

Susan Bal, Luciano J Costa

引用次数: 0

Venetoclax-Based Combination Regimens in Acute Myeloid Leukemia. 基于 Venetoclax 的急性髓性白血病联合疗法

IF 11.5

Blood Cancer Discovery Pub Date : 2024-11-20 DOI: 10.1158/2643-3230.BCD-24-0171

Hannah Goulart, Hagop Kantarjian, Naveen Pemmaraju, Naval Daver, Courtney D DiNardo, Caitlin R Rausch, Farhad Ravandi, Tapan M Kadia

引用次数: 0

T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma: Optimal Dosing Schedule and Duration of Treatment. 治疗多发性骨髓瘤的 T 细胞重定向双特异性抗体：最佳用药方案和疗程。

IF 11.5

Blood Cancer Discovery Pub Date : 2024-11-01 DOI: 10.1158/2643-3230.BCD-24-0124

Niels W C J van de Donk, Leo Rasche, Surbhi Sidana, Sonja Zweegman, Alfred L Garfall

{"title":"T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma: Optimal Dosing Schedule and Duration of Treatment.","authors":"Niels W C J van de Donk, Leo Rasche, Surbhi Sidana, Sonja Zweegman, Alfred L Garfall","doi":"10.1158/2643-3230.BCD-24-0124","DOIUrl":"10.1158/2643-3230.BCD-24-0124","url":null,"abstract":"T cell-redirecting bispecific antibodies (BsAb) induce significant responses in heavily pretreated multiple myeloma. BsAbs are currently administered in a dose-dense manner until disease progression. However, continuous therapy is associated with safety concerns, including a high risk of infections and high costs. In addition, chronic exposure to BsAbs, and thus long-term T-cell stimulation, induces T-cell exhaustion, which may contribute to relapse. There is increasing evidence that the strategy of induction treatment followed by maintenance with longer intervals between BsAb doses, or limited treatment duration with cessation of therapy in patients who achieve deep remission, improves the balance between toxicity and efficacy. Significance: There is increasing evidence that after initial debulking, less-frequent BsAb administration mitigates T-cell exhaustion and minimizes the potential for chronic or cumulative toxicity while maintaining durable clinical responses. In addition, specific patient subsets may experience an extended treatment-free period following fixed-duration treatment. Fixed-duration treatment may, therefore, decrease cumulative toxicities and the burden on patients and healthcare systems.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"388-399"},"PeriodicalIF":11.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tracking Rare Single Donor and Recipient Immune and Leukemia Cells after Allogeneic Hematopoietic Cell Transplantation Using Mitochondrial DNA Mutations. 利用线粒体 DNA 突变追踪异体造血细胞移植后罕见的单个供体和受体免疫细胞和白血病细胞。

IF 11.5

Blood Cancer Discovery Pub Date : 2024-11-01 DOI: 10.1158/2643-3230.BCD-23-0138

Livius Penter, Nicoletta Cieri, Katie Maurer, Marwan Kwok, Haoxiang Lyu, Wesley S Lu, Giacomo Oliveira, Satyen H Gohil, Ignaty Leshchiner, Caleb A Lareau, Leif S Ludwig, Donna S Neuberg, Haesook T Kim, Shuqiang Li, Lars Bullinger, Jerome Ritz, Gad Getz, Jacqueline S Garcia, Robert J Soiffer, Kenneth J Livak, Catherine J Wu

{"title":"Tracking Rare Single Donor and Recipient Immune and Leukemia Cells after Allogeneic Hematopoietic Cell Transplantation Using Mitochondrial DNA Mutations.","authors":"Livius Penter, Nicoletta Cieri, Katie Maurer, Marwan Kwok, Haoxiang Lyu, Wesley S Lu, Giacomo Oliveira, Satyen H Gohil, Ignaty Leshchiner, Caleb A Lareau, Leif S Ludwig, Donna S Neuberg, Haesook T Kim, Shuqiang Li, Lars Bullinger, Jerome Ritz, Gad Getz, Jacqueline S Garcia, Robert J Soiffer, Kenneth J Livak, Catherine J Wu","doi":"10.1158/2643-3230.BCD-23-0138","DOIUrl":"10.1158/2643-3230.BCD-23-0138","url":null,"abstract":"Combined tracking of clonal evolution and chimeric cell phenotypes could enable detection of the key cellular populations associated with response following therapy, including after allogeneic hematopoietic stem cell transplantation (HSCT). We demonstrate that mitochondrial DNA (mtDNA) mutations coevolve with somatic nuclear DNA mutations at relapse post-HSCT and provide a sensitive means to monitor these cellular populations. Furthermore, detection of mtDNA mutations via single-cell assay for transposase-accessible chromatin with select antigen profiling by sequencing (ASAP-seq) simultaneously determines not only donor and recipient cells but also their phenotype at frequencies of 0.1% to 1%. Finally, integration of mtDNA mutations, surface markers, and chromatin accessibility profiles enables the phenotypic resolution of leukemic populations from normal immune cells, thereby providing fresh insights into residual donor-derived engraftment and short-term clonal evolution following therapy for post-transplant leukemia relapse. As throughput evolves, we envision future development of single-cell sequencing-based post-transplant monitoring as a powerful approach for guiding clinical decision-making. Significance: mtDNA mutations enable single-cell tracking of leukemic clonal evolution and donor-recipient origin following allogeneic HSCT. This provides unprecedented insight into chimeric cellular phenotypes of early immune reconstitution, incipient relapse, and quality of donor engraftment with immediate translational potential for future clinical post-transplant monitoring and decision-making.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"442-459"},"PeriodicalIF":11.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A View of Myeloid Transformation through the Hallmarks of Cancer. 从癌症的标志看髓细胞转化。

IF 11.5

Blood Cancer Discovery Pub Date : 2024-11-01 DOI: 10.1158/2643-3230.BCD-24-0009

Inés Fernández-Maestre, Sheng F Cai, Ross L Levine

{"title":"A View of Myeloid Transformation through the Hallmarks of Cancer.","authors":"Inés Fernández-Maestre, Sheng F Cai, Ross L Levine","doi":"10.1158/2643-3230.BCD-24-0009","DOIUrl":"10.1158/2643-3230.BCD-24-0009","url":null,"abstract":"The development of myeloid malignancies is influenced by a range of cell-intrinsic and cell-extrinsic factors, which can be conceptualized using the hallmarks of cancer. Although many facets of myeloid transformation are similar to those in solid tumors, there are also notable differences. Unlike solid tumors, hematologic malignancies typically exhibit fewer genetic mutations, which have been well characterized. However, understanding the cell-extrinsic factors contributing to myeloid malignancies can be challenging due to the complex interactions in the hematopoietic microenvironment. Researchers need to focus on these intricate factors to prevent the early onset of myeloid transformation and develop appropriate interventions. Significance: Myeloid malignancies are common in the elderly, and acute myeloid leukemia has an adverse prognosis in older patients. Investigating cell-extrinsic factors influencing myeloid malignancies is crucial to developing approaches for preventing or halting disease progression and predicting clinical outcomes in patients with advanced disease. Whereas successful intervention may require targeting various mechanisms, understanding the contribution of each cell-extrinsic factor will help prioritize clinical targets.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"377-387"},"PeriodicalIF":11.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0