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Cells
Special Issues
Adoptive Cell Therapy against Cancers
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Adoptive Cell Therapy against Cancers

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 7131

Special Issue Editors

Dr. Lei Wang

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Guest Editor
Department of Internal Medicine V, Universitätsklinikum Heidelberg, Heidelberg, Germany
Interests: celullar therapy; GMP; analytical method development and validation; immune tolerance
Dr. Sanmei Wang

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Guest Editor
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
Interests: immunotherapy; chimeric antigen receptor therapy; T cell receptor signaling
Dr. Wenjie Gong

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Guest Editor
Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
Interests: immunotherapy; cancer

Special Issue Information

Dear Colleagues,

Adoptive cell therapy (ACT), especially, chimeric antigen receptor (CAR) T cell therapy, is rapidly growing and have revolutionized the field of immunotherapy for cancer, showing promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. However, many challenges limit the therapeutic efficacy of ACT in solid tumors and hematological malignancies. Barriers to effective ACT include time-consuming and lab-intensive manufacturing, complex logistics, severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration, and so on. To overcome these hurdles, several strategies, from screening the best starting material, developing novel CAR or TCR structures and improving the manufacturing process up to combining ACT with other anti-tumor agents, could be considered to optimize the clinical efficacy of ACT.

This Special Issue aims to cover recent advances in adoptive cell therapy including manufacturing, method validation for product specification, logistics study, novel CAR design, combination therapy and clinical trials and therefore seeks for review or original manuscripts addressing one of the aforementioned (or related) topics.

We look forward to receiving your contributions.

Dr. Lei Wang
Dr. Sanmei Wang
Dr. Wenjie Gong
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. Cells 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 2700 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 cells
  • TCR-T cells
  • CAR-NK cells
  • cellular therapies
  • combination therapy
  • CAR design
  • targeted therapy
  • small molecules
  • manufacturing, methods and specification

Published Papers (4 papers)

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Research

20 pages, 4465 KiB  
Article
Safety and Efficacy of Humanized Versus Murinized CD19 and CD22 CAR T-Cell Cocktail Therapy for Refractory/Relapsed B-Cell Lymphoma
by Lefu Huang, Jingjing Li, Junfang Yang, Xian Zhang, Min Zhang, Jiujiang He, Gailing Zhang, Wenqian Li, Hui Wang, Jianqiang Li and Peihua Lu
Cells 2022, 11(24), 4085; https://doi.org/10.3390/cells11244085 - 16 Dec 2022
Cited by 3 | Viewed by 1880
Abstract
CD19 chimeric antigen receptor T-cell (CAR-T) therapy is efficacious for refractory/relapsed (R/R) B-cell hematological malignancies, yet relapse due to CD19 antigen escape remains a challenge. Our trial explored simultaneous targeting of multiple B-cell antigens as a therapeutic approach that may reduce the risk [...] Read more.
CD19 chimeric antigen receptor T-cell (CAR-T) therapy is efficacious for refractory/relapsed (R/R) B-cell hematological malignancies, yet relapse due to CD19 antigen escape remains a challenge. Our trial explored simultaneous targeting of multiple B-cell antigens as a therapeutic approach that may reduce the risk of relapse. We tested the safety and efficacy of CAR19/22 T-cell cocktail therapy including murinized and humanized products among patients with R/R aggressive B-cell lymphoma. In the group that received the humanized product, 11/12 (91.7%) patients achieved an objective response, including 9/12 (75%) complete responses (CRs) by day 28. The overall response rate and CR rate in the murinized group was 92.9% (13/14) and 42.9% (6/14), respectively. Nine of 12 (75%) patients in the humanized group maintained CR at month 3 following infusion, compared to 5/14 patients (35.7%) in the murinized group. Progression-free survival (PFS) was more favorable in the humanized compared to the murinized group. Most patients had mild cytokine release syndrome (CRS) (grade 1–2) in both groups. This study demonstrates that CAR19/22 T-cell cocktail therapy is safe and effective for R/R B-cell lymphoma and that patients treated with a humanized CAR-T exhibited better efficacy compared to patients treated with a murinized CAR-T therapy. Full article
(This article belongs to the Special Issue Adoptive Cell Therapy against Cancers)
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11 pages, 2753 KiB  
Article
RAC1, a Potential Diagnostic and Prognostic Marker for Diffuse Large B Cell Lymphoma
by Xue Wu, Yuan Li, Wandong Zhang, Jing Zhang, Baoan Chen and Zheng Ge
Cells 2022, 11(24), 4039; https://doi.org/10.3390/cells11244039 - 14 Dec 2022
Viewed by 1510
Abstract
The gene changes for diagnosis and prognosis of diffuse large B cell lymphoma (DLBCL) still remain unclear. RAC1 was reported to be asso;ciated with the B cell receptor signal pathway, but its relations with DLBCL have not yet been systematically explored. In this [...] Read more.
The gene changes for diagnosis and prognosis of diffuse large B cell lymphoma (DLBCL) still remain unclear. RAC1 was reported to be asso;ciated with the B cell receptor signal pathway, but its relations with DLBCL have not yet been systematically explored. In this study, we have conducted molecular, bioinformatics and clinical analyses by using publicly available data from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and logistic regression were performed to evaluate the association between RAC1 and clinical features in patients. Kaplan–Meier and Cox regression methods were used to examine the impacts of RAC1 expression level on overall survival, and a nomogram was performed to illustrate the correlation between RAC1 and the risk of DLBCL. Our results revealed that the expression level of RAC1 in DLBCL was higher than that in normal tissues or lymphadenitis. High-level expression of RAC1 was significantly associated with clinical stage, as well as being an independent factor affecting overall survival. RAC1 was negatively correlated with Bruton’s tyrosine kinase (BTK). The association between RAC1 gene expression and the risk of DLBCL was presented in a nomogram. In conclusion, RAC1 expression patterns may be used to predict the development and prognosis of DLBCL. Full article
(This article belongs to the Special Issue Adoptive Cell Therapy against Cancers)
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14 pages, 3621 KiB  
Article
Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing Rag1 Knock-Out Mice
by Seon-Hee Kim, Eun Mi Go, Dong Hoon Shin, Beom K. Choi and Chungyong Han
Cells 2022, 11(23), 3894; https://doi.org/10.3390/cells11233894 - 2 Dec 2022
Viewed by 1620
Abstract
In adoptive T cell therapy (ACT), the transfer of tumor-specific T cells is paralleled by the conditioning regimen to increase therapeutic efficacy. Pre-conditioning depletes immune-suppressive cells and post-conditioning increases homeostatic signals to improve the persistence of administered T cells. Identifying the favorable immunological [...] Read more.
In adoptive T cell therapy (ACT), the transfer of tumor-specific T cells is paralleled by the conditioning regimen to increase therapeutic efficacy. Pre-conditioning depletes immune-suppressive cells and post-conditioning increases homeostatic signals to improve the persistence of administered T cells. Identifying the favorable immunological factors involved in a conditioning regimen is important to design effective strategies in ACT. Here, by using an ACT model of murine melanoma, we evaluate the effect of the total body irradiation (TBI) and interleukin-2 (IL-2) treatment combination. The use of a Rag1 knock-out strain, which lacks endogenous T cells, enables the identification of factors in a way that focuses more on transferred T cells. We demonstrate that the TBI/IL-2 combination has no additive effect in ACT, although each conditioning improves the therapeutic outcome. While the combination increases the frequency of transferred T cells in lymphoid and tumor tissues, the activation intensity of the cells is reduced compared to that of the sole TBI treatment. Notably, we show that in the presence of TBI, the IL-2 treatment reduces the frequency of intra-tumoral dendritic cells, which are crucial for T cell activation. The current study provides insights into the immunological events involved in the TBI/IL-2 combination in ACT. Full article
(This article belongs to the Special Issue Adoptive Cell Therapy against Cancers)
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17 pages, 4846 KiB  
Article
The Ion Channel Gene KCNAB2 Is Associated with Poor Prognosis and Loss of Immune Infiltration in Lung Adenocarcinoma
by Yin Lyu, Qiao Wang, Jingtian Liang, Li Zhang and Hao Zhang
Cells 2022, 11(21), 3438; https://doi.org/10.3390/cells11213438 - 31 Oct 2022
Cited by 5 | Viewed by 1702
Abstract
The malignancy with the greatest global mortality rate is lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype. The evidence demonstrated that voltage-gated potassium channel subunit beta-2 (KCNAB2) significantly participated in the initiation of colorectal cancer and its progression. However, the biological [...] Read more.
The malignancy with the greatest global mortality rate is lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype. The evidence demonstrated that voltage-gated potassium channel subunit beta-2 (KCNAB2) significantly participated in the initiation of colorectal cancer and its progression. However, the biological function of KCNAB2 in LUAD and its effect on the tumor immune microenvironment are still unknown. In this study, we found that the expression of KCNAB2 in tissues of patients with LUAD was markedly downregulated, and its downregulation was linked to accelerated cancer growth and poor clinical outcomes. In addition, low KCNAB2 expression was correlated with a deficiency in immune infiltration. The mechanism behind this issue might be that KCNAB2 influenced the immunological process such that the directed migration of immune cells was affected. Furthermore, overexpression of KCNAB2 in cell lines promoted the expression of CCL2, CCL3, CCL4, CCL18, CXCL9, CXCL10, and CXCL12, which are necessary for the recruitment of immune cells. In conclusion, KCNAB2 may play a key function in immune infiltration and can be exploited as a predictive biomarker for evaluating prognosis and a possible immunotherapeutic target. Full article
(This article belongs to the Special Issue Adoptive Cell Therapy against Cancers)
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