Submit to Cancers Review for Cancers Propose a Special Issue

Journal Menu

Journal Browser

Advances in Immunotherapy for Hematological Malignancies

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 29496

Share This Special Issue

Special Issue Editors

Dr. Anilkumar Gopalakrishnapillai

E-Mail Website
Guest Editor

Center for Cancer and Blood Disorders, Nemours Children’s Health System, Wilmington, DE 19803, USA
Interests: hematological neoplasms; immunotherapy; drug resistance; leukemic niche; cancer stem cells

Dr. Jonathan Fisher

E-Mail Website
Guest Editor

1. Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
2. Department of Oncology, Great Ormond Street Hospital, London WC1N 3JH, UK
Interests: cellular immunotherapy; gamma-delta T-cells; innate immune cell engineering; solid tumour targeting

Dr. Raju K. Pillai

E-Mail Website
Guest Editor

Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA
Interests: hematopathology; molecular pathology; lymphoma; leukemia; genomics; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Wish you all a very happy and productive new year 2022!

Hematopoiesis is a process of generating fully functional blood cells while maintaining the pool of hematopoietic stem cells in the bone marrow niche. Unlike many other cell types, blood cells undergo large number of cell divisions and therefore face the risk of acquiring somatic mutations. Such changes in the hematopoietic cells, including stem cells, eventually lead to hematological neoplasms (HMs), via poorly understood mechanisms. On a positive note, a vast improvement in the treatment options led to a better clinical outcome in some types of HMs. Immunotherapy has emerged as one of the major treatment options for hematological malignancies (HMs). Substantial progress achieved in this field was accompanied by many challenges, specifically therapy resistance and acute toxicity. The purpose of this Special Issue is to highlight advancements in various immunotherapeutic approaches to improve clinical outcome among patients with HMs. Emphasis will also be given on novel strategies to enhance the efficacy of immunotherapeutic treatment using rational combinations to overcome the resistance and curb side effects by finetuning immune function. Reviews and general articles focusing on the exciting immunotherapeutic developments in leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma, myeloproliferative neoplasm, and other hematological malignancies, including precancerous lesions, are invited. These studies can include both in vitro and in vivo studies for preclinical testing, clinical trials, or efforts to delineate mechanisms of treatment resistance.

In this issue, we are inviting original articles/focused reviews reporting such advancements that change the landscape of treatment for hematological malignancies. These articles are not limited to approaches such as chimeric antigen receptor (CAR) T-cells (CAR-T), CAR macrophages (CAR-Ma), CAR natural killer cells (CAR-NK), UltraCAR-T, and bispecific T cell engagers (BiTES) but also include drug immunoconjugate, cancer vaccine, and various combination strategies to improve the efficacy or avoid immunotherapy-based treatment resistance.

Dr. Anilkumar Gopalakrishnapillai
Dr. Jonathan Fisher
Dr. Raju K. Pillai
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 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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

immunotherapy
hematological malignancies
CAR-T
BiTEs
CAR-NK
CAR-Ma
UltraCART
DNA vaccine
immunoconjugate
combination therapies
immune checkpoint blockade

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (8 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

10 pages, 1056 KiB

Open AccessArticle

The Acquisition of Complement-Dependent Cytotoxicity by the Type II Anti-CD20 Therapeutic Antibody Obinutuzumab

by Alicja Kuźniewska, Alan Majeranowski, Sara Henry, Daria Kowalska, Grzegorz Stasiłojć, Aleksandra Urban, Jan M. Zaucha and Marcin Okrój

Cancers 2024, 16(1), 49; https://doi.org/10.3390/cancers16010049 - 21 Dec 2023

Cited by 1 | Viewed by 1474

Abstract

Rituximab, a prototypic anti-CD20 mAb, and the third-generation anti-CD20 mAb obinutuzumab differ in their ability to activate the complement system. According to recent studies, this contrast stems from the architecture of the antigen–antibody complex formed by these two mAbs that facilitates (rituximab) or disables (obinutuzumab) further oligomerization, leading to engagement of the initial classical complement pathway component C1q. We examined whether a gain-of-function C2 variant that acts downstream of C1q and enforces the formation of complement convertase resistant to physiological decay can impact complement activation by obinutuzumab. Co-application of the C2 variant with obinutuzumab and human serum resulted in complement-dependent cytotoxicity equal to or higher than attainable for rituximab. This effect was observed either in serum or hirudin-anticoagulated whole blood. Long-term (24 h) overall cytotoxicity of obinutuzumab was improved in target cells of moderate sensitivity to complement but diminished in cells of low sensitivity. Our results demonstrate that the ability of complement activation of a given antibody is not ultimately determined at the stage of initial interactions with its target antigen but is modulable at later stages of the cascade and that the benefit of the acquisition of this new effector mechanism by obinutuzumab depends on the target cell characteristics. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

► Show Figures

Figure 1

20 pages, 6576 KiB

Open AccessArticle

mAb14, a Monoclonal Antibody against Cell Surface PCNA: A Potential Tool for Sezary Syndrome Diagnosis and Targeted Immunotherapy

by Jamal Knaneh, Emmilia Hodak, Shlomit Fedida-Metula, Avishay Edri, Rachel Eren, Yael Yoffe, Iris Amitay-Laish, Hadas Prag Naveh, Ido Lubin, Angel Porgador and Lilach Moyal

Cancers 2023, 15(17), 4421; https://doi.org/10.3390/cancers15174421 - 4 Sep 2023

Cited by 2 | Viewed by 3310

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of cancer cells (csPCNA), but not on normal cells. It functions as an immune checkpoint ligand by interacting with natural killer (NK) cells through the NK inhibitory receptor NKp44, leading to the inhibition of NK cytotoxicity. A monoclonal antibody (mAb14) was established to detect csPCNA on cancer cells and block their interaction with NKp44. In this study, three CTCL cell lines and peripheral blood mononuclear cells (PBMCs) from patients with SS and healthy donors were analyzed for csPCNA using mAb14, compared to monoclonal antibody PC10, against nuclear PCNA (nPCNA). The following assays were used: immunostaining, imaging flow cytometry, flow cytometry, cell sorting, cell cycle analysis, ELISA, and the NK-cell cytotoxic assay. mAb14 successfully detected PCNA on the membrane and in the cytoplasm of viable CTCL cell lines associated with the G2/M phase. In the Sézary PBMCs, csPCNA was expressed on lymphoma cells that had an atypical morphology and not on normal cells. Furthermore, it was not expressed on PBMCs from healthy donors. In the co-culture of peripheral blood NK (pNK) cells with CTCL lines, mAb14 increased the secretion of IFN-γ, indicating the reactivation of pNK activity. However, mAb14 did not enhance the cytotoxic activity of pNK cells against CTCL cell lines. The unique expression of csPCNA detected by mAb14 suggests that csPCNA and mAb14 may serve as a potential biomarker and tool, respectively, for detecting malignant cells in SS and possibly other CTCL variants. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

► Show Figures

Figure 1

14 pages, 1016 KiB

Open AccessArticle

Timely Leukapheresis May Interfere with the “Fitness” of Lymphocytes Collected for CAR-T Treatment in High Risk DLBCL Patients

by Mirko Farina, Marco Chiarini, Camillo Almici, Eugenia Accorsi Buttini, Francesco Zuccalà, Simone Piva, Irene Volonghi, Loris Poli, Simona Bernardi, Federica Colnaghi, Federica Re, Alessandro Leoni, Nicola Polverelli, Alessandro Turra, Enrico Morello, Anna Galvagni, Daniele Moratto, Duilio Brugnoni, Chiara Cattaneo, Emilio Ferrari, Andrea Bianchetti, Michele Malagola, Alessandro Re and Domenico Russo Show full author list Hide full author list

Cancers 2022, 14(21), 5276; https://doi.org/10.3390/cancers14215276 - 27 Oct 2022

Cited by 3 | Viewed by 2223

Abstract

The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases. However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (ClinicalTrials.gov: NCT05366569) is to improve our understanding of the lymphocyte harvest to maximize the quality of the CAR-T cell product. Of the 14 patients enrolled, 11 were diagnosed with DLBCL, 2 with PMBCL, and 1 with ALL. Five of 11 DLBCL patients met the criteria for “pre-emptive” Lymphocytes-apheresis (being at high risk of second relapse), and 6 were included in the standard-of-care Lymphocytes-apheresis group. Previous autologous stem cell transplantation (ASCT) and age were significantly different between the two groups. At the time of Lymphocyte-apheresis, patients in the “pre-emptive” group had more “fit” lymphocytes (higher CD4+/CD8+ ratio; higher naïve T cells levels) compared with standard group, probably due to the impact of ASCT. At the same time, also being older than 60 years results in a more “exhausted” lymphocyte profile. Overall, “pre-emptive” Ly-apheresis in DLBCL patients at high risk of relapse appears to be feasible and may allow the timely collection of “fit” lymphocytes for CAR-T cell manufacturing. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

► Show Figures

Figure 1

11 pages, 1492 KiB

Open AccessArticle

CD73 Promotes Chronic Lymphocytic Leukemia

by David Allard, Pavel Chrobak, Yacine Bareche, Bertrand Allard, Priscilla Tessier, Marjorie A. Bergeron, Nathalie A. Johnson and John Stagg

Cancers 2022, 14(13), 3130; https://doi.org/10.3390/cancers14133130 - 26 Jun 2022

Cited by 3 | Viewed by 2339

Abstract

The ecto-nucleotidase CD73 is an important immune checkpoint in tumor immunity that cooperates with CD39 to hydrolyze pro-inflammatory extracellular ATP into immunosuppressive adenosine. While the role of CD73 in immune evasion of solid cancers is well established, its role in leukemia remains unclear. To investigate the role of CD73 in the pathogenesis of chronic lymphocytic leukemia (CLL), Eµ-TCL1 transgenic mice that spontaneously develop CLL were crossed with CD73^−/− mice. Disease progression in peripheral blood and spleen, and CLL markers were evaluated by flow cytometry and survival was compared to CD73-proficient Eµ-TCL1 transgenic mice. We observed that CD73 deficiency significantly delayed CLL progression and prolonged survival in Eµ-TCL1 transgenic mice, and was associated with increased accumulation of IFN-γ⁺ T cells and effector-memory CD8⁺ T cells. Neutralizing IFN-γ abrogated the survival advantage of CD73-deficient Eµ-TCL1 mice. Intriguingly, the beneficial effects of CD73 deletion were restricted to male mice. In females, CD73 deficiency was uniquely associated with the upregulation of CD39 in normal lymphocytes and sustained high PD-L1 expression on CLL cells. In vitro studies revealed that adenosine signaling via the A2a receptor enhanced PD-L1 expression on Eµ-TCL1-derived CLL cells, and a genomic analysis of human CLL samples found that PD-L1 correlated with adenosine signaling. Our study, thus, identified CD73 as a pro-leukemic immune checkpoint in CLL and uncovered a previously unknown sex bias for the CD73-adenosine pathway. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

► Show Figures

Figure 1

Review

Jump to: Research

15 pages, 312 KiB

Open AccessReview

Clinical PD-1/PD-L1 Blockades in Combination Therapies for Lymphomas

by Hiroo Katsuya, Junji Suzumiya and Shinya Kimura

Cancers 2023, 15(22), 5399; https://doi.org/10.3390/cancers15225399 - 14 Nov 2023

Cited by 2 | Viewed by 2451

Abstract

Immunotherapy with the programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) blockade has revolutionized the treatment of advanced solid cancers. However, these clinical benefits have been limited to cases of malignant lymphomas, showing promising results for only classic Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBCL). To bring clinical benefits to more patients with lymphoma, numerous combination therapies involving PD-1/PD-L1 blockade have been tested in clinical trials in both frontline and relapsed/refractory settings. This article reviews the current landscape of combination therapies with PD-1/PD-L1 blockade for lymphoma and discusses the potential therapeutic approaches. An interim analysis of a phase 3 study demonstrated increased progression-free survival with nivolumab combination therapy over the current frontline treatment in patients with advanced-stage cHL. The results of combination therapies for aggressive B-cell lymphomas, except for PMBCL, have been disappointing. Several clinical trials of combined PD-1/PD-L1 blockade and Bruton’s tyrosine kinase inhibitors are exploring its efficacy in patients with chronic lymphocytic leukemia (CLL) with Richter transformation. Several T-cell lymphoma subtypes respond to PD-1/PD-L1 blockade monotherapy. Further clinical trials are underway to investigate appropriate combination regimens with PD-1/PD-L1 blockade, especially for cHL, CLL with Richter transformation, and T-cell lymphoma, in both frontline and relapsed/refractory settings. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

30 pages, 2273 KiB

Open AccessReview

Bispecific Antibodies in Hematological Malignancies: A Scoping Review

by Mohamed H. Omer, Areez Shafqat, Omar Ahmad, Khaled Alkattan, Ahmed Yaqinuddin and Moussab Damlaj

Cancers 2023, 15(18), 4550; https://doi.org/10.3390/cancers15184550 - 14 Sep 2023

Cited by 9 | Viewed by 4501

Abstract

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgkin’s lymphoma, acute myelogenous leukemia, and acute lymphoblastic leukemia. However, despite their generally favorable safety profiles, particular toxicities such as infections, cytokine release syndrome, myelosuppression, and neurotoxicity after BiAb/BiTE therapy raise valid concerns. Moreover, target antigen loss and the immunosuppressive microenvironment of hematological neoplasms facilitate resistance towards BiTEs/BiAbs. This review aims to highlight the most recent evidence from clinical trials evaluating the safety and efficacy of BiAbs/BiTEs. Additionally, the review will provide mechanistic insights into the limitations of BiAbs whilst outlining practical applications and strategies to overcome these limitations. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

► Show Figures

Figure 1

15 pages, 1230 KiB

Open AccessReview

Non-Conventional Allogeneic Anti-BCMA Chimeric Antigen Receptor-Based Immune Cell Therapies for Multiple Myeloma Treatment

by Zhicheng Du, Sumin Zhu, Xi Zhang, Zhiyuan Gong and Shu Wang

Cancers 2023, 15(3), 567; https://doi.org/10.3390/cancers15030567 - 17 Jan 2023

Cited by 8 | Viewed by 2570

Abstract

MM, characterized by the progressive accumulation of clonal plasma cells in bone marrow, remains a severe medical problem globally. Currently, almost all MM patients who have received standard treatments will eventually relapse. Autologous anti-BCMA CAR-T cells are one of the FDA-approved immunotherapy cell-based products for treating adults with relapsed or refractory (r/r) multiple myeloma. However, this type of CAR-T cell product has several limitations, including high costs, long manufacturing times, and possible manufacturing failure, which significantly hinder its wider application for more patients. In this review, we summarized the current development stage of applying other types of immune cells to bring the anti-BCMA CAR-T therapy from autologous to allogeneic. In general, anti-BCMA CAR gene-edited αβ T cells and CAR-Natural Killer (NK) cells are at the forefront, with multiple clinical trials ongoing, while CAR-γδ T cells and CAR-invariant Natural Killer T (iNKT) cells are still in pre-clinical studies. Other immune cells such as macrophages, B cells, and dendritic cells have been mainly developed to target other antigens and have the potential to be used to target BCMA. Nevertheless, additional regulatory requirements might need to be taken into account in developing these non-conventional allogenic anti-BCMA CAR-based cell products. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

► Show Figures

Figure 1

18 pages, 1147 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Mesothelin: An Immunotherapeutic Target beyond Solid Tumors

by Joshua R. Faust, Darcy Hamill, Edward Anders Kolb, Anilkumar Gopalakrishnapillai and Sonali P. Barwe

Cancers 2022, 14(6), 1550; https://doi.org/10.3390/cancers14061550 - 18 Mar 2022

Cited by 31 | Viewed by 9318

Abstract

Modern targeted cancer therapies rely on the overexpression of tumor associated antigens with very little to no expression in normal cell types. Mesothelin is a glycosylphosphatidylinositol-anchored cell surface protein that has been identified in many different tumor types, including lung adenocarcinomas, ovarian carcinomas, and most recently in hematological malignancies, including acute myeloid leukemia (AML). Although the function of mesothelin is widely unknown, interactions with MUC16/CA125 indicate that mesothelin plays a role in the regulation of proliferation, growth, and adhesion signaling. Most research on mesothelin currently focuses on utilizing mesothelin to design targeted cancer therapies such as monoclonal antibodies, antibody–drug conjugates, chimeric antigen receptor T and NK cells, bispecific T cell engaging molecules, and targeted alpha therapies, amongst others. Both in vitro and in vivo studies using different immunotherapeutic modalities in mesothelin-positive AML models highlight the potential impact of this approach as a unique opportunity to treat hard-to-cure AML. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

► Show Figures

Journal Menu

Journal Browser

Advances in Immunotherapy for Hematological Malignancies

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI