Submit to Cancers Review for Cancers Propose a Special Issue

Journal Browser

Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer

Special Issue Editors
Special Issue Information
Keywords
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 (15 June 2023) | Viewed by 38963

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer book cover image

Share This Special Issue

Special Issue Editor

Dr. Vita Golubovskaya

E-Mail Website
Guest Editor

1. Research and Business Development, Promab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA
2. Department of Medicine, University of Oklahoma, Oklahoma, OK 73126, USA
Interests: immunotherapy; CAR-T cells; tumor microenvironment; checkpoint protein; hypoxia; tumor survival signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Recently cell therapy became one of the important therapies against different hematological and solid tumors. Cell therapies such as CAR (chimeric antigen receptor)-T, CAR gamma delta T cells, CAR-NK (natural killer) cells and CAR-MA (CAR-macrophages) demonstrated positive results in clinic. These therapies can be autologous or allogeneic using genetically engineered effector cells. The cell therapies can be combined with checkpoint inhibitors against solid tumors to additionally increase their efficacy.

Another very promising therapy against cancer is a therapy with bispecific antibodies engaging T cells or other types of effector cells against cancer. BITEs targeting CD19 antigen are used in clinic against hematological cancers and different designs of bispecific antibodies focused on other targets are used for different types of cancer. Combination of cell therapy with bispecific antibodies and checkpoint inhibitors can be effective way to target tumor and the tumor microenvironment.

Different checkpoint inhibitor antibodies targeting PD-1/PD-L1, LAG3, TIM-3, TIGIT and other pathways recently showed very promising results in clinic.

All these approaches with intracellular signaling, genomics studies, preclinical and clinical results can be used for this issue.

Dr. Vita Golubovskaya
Guest Editor

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. 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

cell therapy
CAR (chimeric antigen receptor)-T
bispecific antibodies engaging T cells
PD-1/PD-L1
LAG3
TIM-3
TIGIT

Published Papers (12 papers)

Download All Papers

Editorial

Jump to: Research, Review

5 pages, 357 KiB

Open AccessEditorial

Editorial on “Cell Therapy, Bispecific Antibodies and Other Immunotherapies against Cancer”

by Vita Golubovskaya

Cancers 2023, 15(20), 5053; https://doi.org/10.3390/cancers15205053 - 19 Oct 2023

Viewed by 819

Abstract

This Special Issue in Cancers, “Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer”, includes interesting reports and reviews on cell therapies and bispecific antibodies [...] Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

Research

Jump to: Editorial, Review

13 pages, 5106 KiB

Open AccessArticle

mRNA-Lipid Nanoparticle (LNP) Delivery of Humanized EpCAM-CD3 Bispecific Antibody Significantly Blocks Colorectal Cancer Tumor Growth

by Vita Golubovskaya, John Sienkiewicz, Jinying Sun, Yanwei Huang, Liang Hu, Hua Zhou, Hizkia Harto, Shirley Xu, Robert Berahovich, Walter Bodmer and Lijun Wu

Cancers 2023, 15(10), 2860; https://doi.org/10.3390/cancers15102860 - 22 May 2023

Cited by 8 | Viewed by 5406

Abstract

The epithelial cell adhesion molecule (EpCAM) is often overexpressed in many types of tumors, including colorectal cancer. We sequenced and humanized an EpCAM mouse antibody and used it to develop bispecific EpCAM-CD3 antibodies. Three different designs were used to generate bispecific antibodies such as EpCAM-CD3 CrossMab knob-in-hole, EpCAM ScFv-CD3 ScFv (BITE), and EpCAM ScFv-CD3 ScFv-human Fc designs. These antibody designs showed strong and specific binding to the EpCAM-positive Lovo cell line and T cells, specifically killed EpCAM-positive Lovo cells and not EpCAM-negative Colo741 cells in the presence of T cells, and increased T cells’ IFN-gamma secretion in a dose-dependent manner. In addition, transfection of HEK-293 cells with EpCAM ScFv-CD3 ScFv human Fc mRNA-LNPs resulted in antibody secretion that killed Lovo cells and did not kill EpCAM-negative Colo741 cells. The antibody increased IFN-gamma secretion against Lovo target cells and did not increase it against Colo741 target cells. EpCAM-CD3 hFc mRNA-LNP transfection of several cancer cell lines (A1847, C30, OVCAR-5) also demonstrated functional bispecific antibody secretion. In addition, intratumoral delivery of the EpCAM-CD3 human Fc mRNA-LNPs into OVCAR-5 tumor xenografts combined with intravenous injection of T cells significantly blocked xenograft tumor growth. Thus, EpCAM-CD3 hFc mRNA-LNP delivery to tumor cells shows strong potential for future clinical studies. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

24 pages, 3885 KiB

Open AccessArticle

TIGIT Expression on Activated NK Cells Correlates with Greater Anti-Tumor Activity but Promotes Functional Decline upon Lung Cancer Exposure: Implications for Adoptive Cell Therapy and TIGIT-Targeted Therapies

by Md Faqrul Hasan, Tayler J. Croom-Perez, Jeremiah L. Oyer, Thomas A. Dieffenthaller, Liza D. Robles-Carrillo, Jonathan E. Eloriaga, Sanjana Kumar, Brendan W. Andersen and Alicja J. Copik

Cancers 2023, 15(10), 2712; https://doi.org/10.3390/cancers15102712 - 11 May 2023

Cited by 4 | Viewed by 2837

Abstract

Treatments targeting TIGIT have gained a lot of attention due to strong preclinical and early clinical results, particularly with anti-PD-(L)1 therapeutics. However, this combination has failed to meet progression-free survival endpoints in phase III trials. Most of our understanding of TIGIT comes from studies of T cell function. Yet, this inhibitory receptor is often upregulated to the same, or higher, extent on NK cells in cancers. Studies in murine models have demonstrated that TIGIT inhibits NK cells and promotes exhaustion, with its effects on tumor control also being dependent on NK cells. However, there are limited studies assessing the role of TIGIT on the function of human NK cells (hNK), particularly in lung cancer. Most studies used NK cell lines or tested TIGIT blockade to reactivate exhausted cells obtained from cancer patients. For therapeutic advancement, a better understanding of TIGIT in the context of activated hNK cells is crucial, which is different than exhausted NK cells, and critical in the context of adoptive NK cell therapeutics that may be combined with TIGIT blockade. In this study, the effect of TIGIT blockade on the anti-tumor activities of human ex vivo-expanded NK cells was evaluated in vitro in the context of lung cancer. TIGIT expression was higher on activated and/or expanded NK cells compared to resting NK cells. More TIGIT⁺ NK cells expressed major activating receptors and exerted anti-tumor response as compared to TIGIT⁻ cells, indicating that NK cells with greater anti-tumor function express more TIGIT. However, long-term TIGIT engagement upon exposure to PVR⁺ tumors downregulated the cytotoxic function of expanded NK cells while the inclusion of TIGIT blockade increased cytotoxicity, restored the effector functions against PVR-positive targets, and upregulated immune inflammation-related gene sets. These combined results indicate that TIGIT blockade can preserve the activation state of NK cells during exposure to PVR⁺ tumors. These results support the notion that a functional NK cell compartment is critical for anti-tumor response and anti-TIGIT/adoptive NK cell combinations have the potential to improve outcomes. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

18 pages, 2850 KiB

Open AccessArticle

Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs

by Elin M. V. Forsberg, Rebecca Riise, Sara Saellström, Joakim Karlsson, Samuel Alsén, Valentina Bucher, Akseli E. Hemminki, Roger Olofsson Bagge, Lars Ny, Lisa M. Nilsson, Henrik Rönnberg and Jonas A. Nilsson

Cancers 2023, 15(3), 648; https://doi.org/10.3390/cancers15030648 - 20 Jan 2023

Cited by 6 | Viewed by 2735

Abstract

Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

14 pages, 2980 KiB

Open AccessArticle

Development of the Novel Bifunctional Fusion Protein BR102 That Simultaneously Targets PD-L1 and TGF-β for Anticancer Immunotherapy

by Zhen-Hua Wu, Na Li, Zhang-Zhao Gao, Gang Chen, Lei Nie, Ya-Qiong Zhou, Mei-Zhu Jiang, Yao Chen, Juan Chen, Xiao-Fen Mei, Feng Hu and Hai-Bin Wang

Cancers 2022, 14(19), 4964; https://doi.org/10.3390/cancers14194964 - 10 Oct 2022

Cited by 7 | Viewed by 2209

Abstract

Immune checkpoint inhibitors (ICIs) are remarkable breakthroughs in treating various types of cancer, but many patients still do not derive long-term clinical benefits. Increasing evidence shows that TGF-β can promote cancer progression and confer resistance to ICI therapies. Consequently, dual blocking of TGF-β and immune checkpoint may provide an effective approach to enhance the effectiveness of ICI therapies. Here, we reported the development and preclinical characterization of a novel bifunctional anti-PD-L1/TGF-β fusion protein, BR102. BR102 comprises an anti-PD-L1 antibody fused to the extracellular domain (ECD) of human TGF-βRII. BR102 is capable of simultaneously binding to TGF-β and PD-L1. Incorporating TGF-βRII into BR102 does not alter the PD-L1 blocking activity of BR102. In vitro characterization further demonstrated that BR102 could disrupt TGF-β-induced signaling. Moreover, BR102 significantly inhibits tumor growth in vivo and exerts a superior antitumor effect compared to anti-PD-L1. Administration of BR102 to cynomolgus monkeys is well-tolerated, with only minimal to moderate and reversing red cell changes noted. The data demonstrated the efficacy and safety of the novel anti-PD-L1/TGF-β fusion protein and supported the further clinical development of BR102 for anticancer therapy. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

13 pages, 2125 KiB

Open AccessArticle

IgG-Based Bispecific Anti-CD95 Antibodies for the Treatment of B Cell-Derived Malignancies and Autoimmune Diseases

by Sebastian Hörner, Moustafa Moustafa-Oglou, Karin Teppert, Ilona Hagelstein, Joseph Kauer, Martin Pflügler, Kristina Neumann, Hans-Georg Rammensee, Thomas Metz, Andreas Herrmann, Helmut R. Salih, Gundram Jung and Latifa Zekri

Cancers 2022, 14(16), 3941; https://doi.org/10.3390/cancers14163941 - 16 Aug 2022

Cited by 2 | Viewed by 2074

Abstract

Antibodies against the B cell-specific antigens CD20 and CD19 have markedly improved the treatment of B cell-derived lymphoma and autoimmune diseases by depleting malignant and autoreactive B cells. However, since CD20 and CD19 are also expressed on healthy B cells, such antibodies lack disease specificity. Here, we optimize a previously developed concept that uses bispecific antibodies to induce apoptosis selectively in malignant and autoreactive B cells that express the death receptor CD95. We describe the development and characterization of bispecific antibodies with CD95xCD20 and CD95xCD19 specificity in a new IgG-based format. We could show that especially the CD95xCD20 antibody mediated a strong induction of apoptosis in malignant B cells in vitro. In vivo, the antibody was clearly superior to the previously used Fabsc format with identical specificities. In addition, both IgGsc antibodies depleted activated B cells in vitro, leading to a significant reduction in antibody production and cytokine secretion. The killing of resting B cells and hepatocytes that lack CD95 and CD20/CD19, respectively, was marginal. Thus, our results imply that bispecific anti-CD95 antibodies in the IgGsc format are an attractive tool for a more selective and efficient depletion of malignant as well as autoreactive B cells. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

14 pages, 615 KiB

Open AccessArticle

Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy

by Simona Gössi, Ulrike Bacher, Claudia Haslebacher, Michael Nagler, Franziska Suter, Cornelia Staehelin, Urban Novak and Thomas Pabst

Cancers 2022, 14(14), 3527; https://doi.org/10.3390/cancers14143527 - 20 Jul 2022

Cited by 10 | Viewed by 1558

Abstract

Background: Due to B-cell aplasia following CAR-T-cell therapy, patients are at risk of severe SARS-CoV-2 course. Methods: COVID-19 vaccines were assessed by IgG antibody tests against SARS-CoV-2 spike protein (anti-S1/S2). Vaccination procedures: group (1): CAR-T-cells followed by two to four vaccine doses; group (2): Two vaccine doses prior to CAR-T-cells, followed by doses 3 or 4. Results: In group 1 (n = 32), 7/30 patients (23.2%) had positive antibody tests after a second dose, 9/23 (39.1%) after a third dose, and 3/3 patients after a fourth dose. A third dose led to seroconversion in 5 of 21 patients (23.8%) with available data, while a fourth dose did so in 2/3 patients. Higher B-cells (AUC: 96.2%, CI: 89–100, p = 0.0006) and lower CAR-T-cell copies (AUC: 77.3%, CI: 57–97, p = 0.0438) were predictive of positive humoral vaccine response. In group 2 (n = 14), 6/14 patients (42.9%) had a positive antibody test after a second dose, 3/8 patients (37.5%) after a third dose, and 3/4 patients after a fourth dose. A third dose led to seroconversion in 1/8 patients (12.5%), while a fourth dose did so in 3/4 patients. Conclusion: Additional vaccine doses increased seroconversion rates whilst high B-cell counts and low CAR-T-cell copy numbers were associated with positive antibody response. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

10 pages, 2566 KiB

Open AccessArticle

Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth

by Lijun Wu, Yanwei Huang, John Sienkiewicz, Jinying Sun, Liselle Guiang, Feng Li, Liming Yang and Vita Golubovskaya

Cancers 2022, 14(10), 2518; https://doi.org/10.3390/cancers14102518 - 20 May 2022

Cited by 3 | Viewed by 3482

Abstract

BCMA antigen is overexpressed in multiple myeloma cells and has been shown to be a promising target for novel cellular and antibody therapeutics. The humanized BCMA (clone 4C8A) antibody that effectively targeted multiple myeloma in a CAR (chimeric antigen receptor) format was used for designing several formats of bispecific BCMA-CD3 antibodies. Several different designs of univalent and bivalent humanized BCMA-CD3 CrossMAB and BCMA-FAB-CD3 ScFv-Fc antibodies were tested for binding with BCMA-positive cells and T cells and for killing by real time cytotoxic activity and IFN-gamma secretion with CHO-BCMA target cells and with multiple myeloma MM1S and H929 cell lines. All BCMA-CD3 antibodies demonstrated specific binding by FACS to CHO-BCMA, multiple myeloma cells, and to T cells with affinity Kd in the nM range. All antibodies with T cells specifically killed CHO-BCMA and multiple myeloma cells in a dose-dependent manner. The BCMA-CD3 antibodies with T cells secreted IFN-gamma with EC₅₀ in the nM range. In addition, three BCMA bispecific antibodies had high in vivo efficacy using an MM1S xenograft NSG mouse model. The data demonstrate the high efficacy of novel hBCMA-CD3 antibodies with multiple myeloma cells and provide a basis for future pre-clinical and clinical development. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

11 pages, 1109 KiB

Open AccessArticle

Glofitamab Treatment in Relapsed or Refractory DLBCL after CAR T-Cell Therapy

by Vera Rentsch, Katja Seipel, Yara Banz, Gertrud Wiedemann, Naomi Porret, Ulrike Bacher and Thomas Pabst

Cancers 2022, 14(10), 2516; https://doi.org/10.3390/cancers14102516 - 20 May 2022

Cited by 16 | Viewed by 4584

Abstract

Chimeric antigen receptor T-cells (CAR T) treatment has become a standard option for patients with diffuse large B-cell lymphomas (DLBCL), which are refractory or relapse after two prior lines of therapy. However, little evidence exists for treatment recommendations in patients who relapse after CAR T-cell treatment and the outcome for such patients is poor. In this study, we evaluated the safety and efficacy of a monotherapy with the bispecific CD20xCD3 antibody glofitamab in patients who progressed after CAR T treatment. We report nine consecutive patients with progressive DLBCL after preceding CAR T-cell therapy. The patients received a maximum of 12 cycles of glofitamab after a single obinutuzumab pre-treatment at an academic institution. CRS was observed in two patients (grade 2 in both patients). We observed an overall response rate of 67%, with four patients achieving a complete response and a partial remission in two patients. Interestingly, we identified increased persistence of circulating CAR T-cells in peripheral blood in three of the five patients with measurable CAR T-cells. Our data suggest that glofitamab treatment is well tolerated and effective in patients with DLBCL relapsing after CAR T-cell therapy and can enhance residual CAR T-cell activity. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

15 pages, 1548 KiB

Open AccessReview

Decoding the Complexity of Immune–Cancer Cell Interactions: Empowering the Future of Cancer Immunotherapy

by Kaitlyn Maffuid and Yanguang Cao

Cancers 2023, 15(16), 4188; https://doi.org/10.3390/cancers15164188 - 21 Aug 2023

Cited by 6 | Viewed by 1977

Abstract

The tumor and tumor microenvironment (TME) consist of a complex network of cells, including malignant, immune, fibroblast, and vascular cells, which communicate with each other. Disruptions in cell–cell communication within the TME, caused by a multitude of extrinsic and intrinsic factors, can contribute to tumorigenesis, hinder the host immune system, and enable tumor evasion. Understanding and addressing intercellular miscommunications in the TME are vital for combating these processes. The effectiveness of immunotherapy and the heterogeneous response observed among patients can be attributed to the intricate cellular communication between immune cells and cancer cells. To unravel these interactions, various experimental, statistical, and computational techniques have been developed. These include ligand–receptor analysis, intercellular proximity labeling approaches, and imaging-based methods, which provide insights into the distorted cell–cell interactions within the TME. By characterizing these interactions, we can enhance the design of cancer immunotherapy strategies. In this review, we present recent advancements in the field of mapping intercellular communication, with a particular focus on immune–tumor cellular interactions. By modeling these interactions, we can identify critical factors and develop strategies to improve immunotherapy response and overcome treatment resistance. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

14 pages, 13627 KiB

Open AccessReview

T-Cell Engagers in Solid Cancers—Current Landscape and Future Directions

by Mohamed Shanshal, Paolo F. Caimi, Alex A. Adjei and Wen Wee Ma

Cancers 2023, 15(10), 2824; https://doi.org/10.3390/cancers15102824 - 18 May 2023

Cited by 2 | Viewed by 3557

Abstract

Monoclonal antibody treatment initially heralded an era of molecularly targeted therapy in oncology and is now widely applied in modulating anti-cancer immunity by targeting programmed cell receptors (PD-1, PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and, more recently, lymphocyte-activation gene 3 (LAG3). Chimeric antigen receptor T-cell therapy (CAR-T) recently proved to be a valid approach to inducing anti-cancer immunity by directly modifying the host’s immune cells. However, such cell-based therapy requires extensive resources such as leukapheresis, ex vivo modification and expansion of cytotoxic T-cells and current Good Manufacturing Practice (cGMP) laboratories and presents significant logistical challenges. Bi-/trispecific antibody technology is a novel pharmaceutical approach to facilitate the engagement of effector immune cells to potentially multiple cancer epitopes, e.g., the recently approved blinatumomab. This opens the opportunity to develop ‘off-the-shelf’ anti-cancer agents that achieve similar and/or complementary anti-cancer effects as those of modified immune cell therapy. The majority of bi-/trispecific antibodies target the tumor-associated antigens (TAA) located on the extracellular surface of cancer cells. The extracellular antigens represent just a small percentage of known TAAs and are often associated with higher toxicities because some of them are expressed on normal cells (off-target toxicity). In contrast, the targeting of intracellular TAAs such as mutant RAS and TP53 may lead to fewer off-target toxicities while still achieving the desired antitumor efficacy (on-target toxicity). Here, we provide a comprehensive review on the emerging field of bi-/tri-specific T-cell engagers and potential therapeutic opportunities. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

27 pages, 1386 KiB

Open AccessEditor’s ChoiceReview

CAR-NK as a Rapidly Developed and Efficient Immunotherapeutic Strategy against Cancer

by Marta Włodarczyk and Beata Pyrzynska

Cancers 2023, 15(1), 117; https://doi.org/10.3390/cancers15010117 - 24 Dec 2022

Cited by 7 | Viewed by 6214

Abstract

Chimeric antigen receptor (CAR)-modified T cell therapy has been rapidly developing in recent years, ultimately revolutionizing immunotherapeutic strategies and providing significant anti-tumor potency, mainly in treating hematological neoplasms. However, graft-versus-host disease (GVHD) and other adverse effects, such as cytokine release syndromes (CRS) and neurotoxicity associated with CAR-T cell infusion, have raised some concerns about the broad application of this therapy. Natural killer (NK) cells have been identified as promising alternative platforms for CAR-based therapies because of their unique features, such as a lack of human leukocyte antigen (HLA)-matching restriction, superior safety, and better anti-tumor activity when compared with CAR-T cells. The lack of CRS, neurotoxicity, or GVHD, in the case of CAR-NK therapy, in addition to the possibility of using allogeneic NK cells as a CAR platform for “off-the-shelf” therapy, opens new windows for strategic opportunities. This review underlines recent design achievements in CAR constructs and summarizes preclinical studies’ results regarding CAR-NK therapies’ safety and anti-tumor potency. Additionally, new approaches in CAR-NK technology are briefly described, and currently registered clinical trials are listed. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (12 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI