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Biomedicines
Special Issues
Cellular and Immunotherapy for Acute Lymphoblastic Leukemia
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Cellular and Immunotherapy for Acute Lymphoblastic Leukemia

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 11316

Special Issue Editors

Dr. Hisham Abdel-Azim

E-Mail Website
Guest Editor
Keck School of Medicine, Children Hospital Los Angeles,University Of Southern California, Los Angeles, CA, USA
Interests: cellular and immunotherapy for ALL
Dr. Rachel Gallant

E-Mail Website
Guest Editor
Children Hospital Los Angeles, Los Angeles, CA, USA
Interests: immunotherapy for ALL
Dr. Kris M. Mahadeo

E-Mail Website
Co-Guest Editor
MD Anderson Cancer Center, University of Texas, Houston, TX, USA
Interests: cellular and immunotherapy for ALL

Special Issue Information

Dear Colleagues,

Acute lymphoblastic leukemia (ALL) affects both adults and children and is the most common pediatric malignancy. ALL is traditionally treated with cytotoxic chemotherapy agents, yet despite improvement in outcomes there is still a subset of patients who do not respond or relapse after chemotherapy. Advances in cellular therapy and immunotherapy provide therapeutic alternatives or adjuncts to chemotherapy which is especially important for those with refractory or relapsed disease. This special issue will explore advances in the pathogenesis of Acute Lymphoblastic Leukemia and cellular and immunotherapy for the treatment of ALL including chimeric antigen receptor T-cell therapy and monoclonal antibody therapy.

Dr. Hisham Abdel-Azim
Dr. Rachel Gallant
Dr. Kris M. Mahadeo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CAR-T
  • Bite
  • NK
  • immunotherapy
  • MoAbs

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Published Papers (3 papers)

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Research

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15 pages, 2582 KiB  
Article
Irinotecan Induces Disease Remission in Xenograft Mouse Models of Pediatric MLL-Rearranged Acute Lymphoblastic Leukemia
by Mark Kerstjens, Patricia Garrido Castro, Sandra S. Pinhanços, Pauline Schneider, Priscilla Wander, Rob Pieters and Ronald W. Stam
Biomedicines 2021, 9(7), 711; https://doi.org/10.3390/biomedicines9070711 - 23 Jun 2021
Cited by 4 | Viewed by 2629
Abstract
Acute lymphoblastic leukemia (ALL) in infants (<1 year of age) remains one of the most aggressive types of childhood hematologic malignancy. The majority (~80%) of infant ALL cases are characterized by chromosomal translocations involving the MLL (or KMT2A) gene, which confer highly [...] Read more.
Acute lymphoblastic leukemia (ALL) in infants (<1 year of age) remains one of the most aggressive types of childhood hematologic malignancy. The majority (~80%) of infant ALL cases are characterized by chromosomal translocations involving the MLL (or KMT2A) gene, which confer highly dismal prognoses on current combination chemotherapeutic regimens. Hence, more adequate therapeutic strategies are urgently needed. To expedite clinical transition of potentially effective therapeutics, we here applied a drug repurposing approach by performing in vitro drug screens of (mostly) clinically approved drugs on a variety of human ALL cell line models. Out of 3685 compounds tested, the alkaloid drug Camptothecin (CPT) and its derivatives 10-Hydroxycamtothecin (10-HCPT) and 7-Ethyl-10-hydroxycamtothecin (SN-38: the active metabolite of the drug Irinotecan) appeared most effective at very low nanomolar concentrations in all ALL cell lines, including models of MLL-rearranged ALL (n = 3). Although the observed in vitro anti-leukemic effects of Camptothecin and its derivatives certainly were not specific to MLL-rearranged ALL, we decided to further focus on this highly aggressive type of leukemia. Given that Irinotecan (the pro-drug of SN-38) has been increasingly used for the treatment of various pediatric solid tumors, we specifically chose this agent for further pre-clinical evaluation in pediatric MLL-rearranged ALL. Interestingly, shortly after engraftment, Irinotecan completely blocked leukemia expansion in mouse xenografts of a pediatric MLL-rearranged ALL cell line, as well as in two patient-derived xenograft (PDX) models of MLL-rearranged infant ALL. Also, from a more clinically relevant perspective, Irinotecan monotherapy was able to induce sustainable disease remissions in MLL-rearranged ALL xenotransplanted mice burdened with advanced leukemia. Taken together, our data demonstrate that Irinotecan exerts highly potent anti-leukemia effects against pediatric MLL-rearranged ALL, and likely against other, more favorable subtypes of childhood ALL as well. Full article
(This article belongs to the Special Issue Cellular and Immunotherapy for Acute Lymphoblastic Leukemia)
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Review

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21 pages, 879 KiB  
Review
The Evolution of Chimeric Antigen Receptor T-Cell Therapy in Children, Adolescents and Young Adults with Acute Lymphoblastic Leukemia
by Dristhi Ragoonanan, Irtiza N. Sheikh, Sumit Gupta, Sajad J. Khazal, Priti Tewari, Demetrios Petropoulos, Shulin Li and Kris M. Mahadeo
Biomedicines 2022, 10(9), 2286; https://doi.org/10.3390/biomedicines10092286 - 14 Sep 2022
Cited by 5 | Viewed by 2649
Abstract
Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary treatment for pediatric, adolescent and young adult patients (AYA) with relapsed/refractory B-cell acute lymphoblastic leukemia. While the landscape of immunotherapy continues to rapidly evolve, widespread use of CAR T therapy is limited and [...] Read more.
Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary treatment for pediatric, adolescent and young adult patients (AYA) with relapsed/refractory B-cell acute lymphoblastic leukemia. While the landscape of immunotherapy continues to rapidly evolve, widespread use of CAR T therapy is limited and many questions remain regarding the durability of CAR T therapy, methods to avoid CAR T therapy resistance and the role of consolidative stem cell transplant. Modified strategies to develop effective and persistent CAR T cells at lower costs and decreased toxicities are warranted. In this review we present current indications, limitations and future directions of CAR T therapy for ALL in the pediatric and AYA population. Full article
(This article belongs to the Special Issue Cellular and Immunotherapy for Acute Lymphoblastic Leukemia)
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19 pages, 1083 KiB  
Review
T-Cell Acute Lymphoblastic Leukemia—Current Concepts in Molecular Biology and Management
by Parveen Shiraz, Waqas Jehangir and Vaibhav Agrawal
Biomedicines 2021, 9(11), 1621; https://doi.org/10.3390/biomedicines9111621 - 4 Nov 2021
Cited by 19 | Viewed by 4993
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric [...] Read more.
T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric intensive regimens and have superior outcomes compared to older adults. In children and young adults, Nelarabine added to frontline chemotherapy improves outcomes and end of consolidation measurable residual disease has emerged as the most valuable prognostic marker. While outcomes for de-novo disease are steadily improving, patients with relapsed and refractory T-ALL fare poorly. Newer targeted therapies are being studied in large clinical trials and have the potential to further improve outcomes. The role of allogeneic stem cell transplant (HSCT) is evolving due to the increased use of pediatric-inspired regimens and MRD monitoring. In this review we will discuss the biology, treatment, and outcomes in pediatric and adult T-ALL. Full article
(This article belongs to the Special Issue Cellular and Immunotherapy for Acute Lymphoblastic Leukemia)
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