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Cancers
Special Issues
Targeted Immunotherapies for Cancers
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Targeted Immunotherapies for Cancers

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

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 17815

Special Issue Editors

Dr. Anthony Cheung

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Guest Editor
1. St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Guy’s Hospital, London SE1 9RT, UK
2. Breast Cancer Now Research Unit, King’s College London, Guy’s Cancer Centre, London SE1 9RT, UK
Interests: triple negative breast cancer; antibody-drug conjugate; antibody targeted therapy; biomarker discovery; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals
Dr. Silvia Crescioli

E-Mail Website
Guest Editor
St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Guy’s Hospital, London SE1 9RT, UK
Interests: melanoma; antibody–drug conjugate; antibody targeted therapy; cancer immunology; immunotherapy; antibody engineering and glycoengineering; B cells
Special Issues, Collections and Topics in MDPI journals
Dr. Alicia Chenoweth

E-Mail Website
Guest Editor
1. St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Guy’s Hospital, London SE1 9RT, UK
2. Breast Cancer Now Research Unit, King’s College London, Guy’s Cancer Centre, London SE1 9RT, UK
Interests: antibody engineering; tumor microenvironment; antibody targeted therapy; cancer immunotherapy; NK cells; cancer immunology

Special Issue Information

Dear Colleagues,

Advancements in immunotherapy have revolutionized cancer treatment in a broad variety of hematological and solid malignancies and rejuvenated the field of cancer immunology. Several types of immunotherapy, including adoptive cell transfer and immune checkpoint inhibitors, have obtained durable clinical responses. Despite their success in immunogenic tumors, due to the substantial heterogeneity of immune target expression and immune cell infiltration in tumor lesions, only subsets of cancer patients currently benefit from these treatments.

Novel preclinical studies and clinical trials are investigating drugs targeting the immune checkpoint axis, either as monotherapy or in combination with other regimens. Clinical results of immunotherapy in low immunogenic cancer types are poor, with modest response rates as low as 5% with monotherapy, especially in unselected patient populations. However, a combination of chemotherapy or targeted therapy together with checkpoint blockade has demonstrated better success. These highlight an urgent unmet need for new immune targets and modification of mAbs for improved clinical function. Immunomodulatory antibodies, bispecific immune cell engagers, and antibodies of alternative isotypes can also present a potential strategy to retain, recruit, or differentially activate various immune effector cells in tumor microenvironments and facilitate immune surveillance and immune system-mediated tumor cell destruction.

This Special Issue will highlight promising immune targeting strategies that may provide the basis for further translational investigations, particularly for patients who do not adequately benefit from currently available therapies.

In this Special Issue, original research articles and reviews are welcome. We look forward to receiving your contributions.

Dr. Anthony Cheung
Dr. Silvia Crescioli
Dr. Alicia Chenoweth
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. 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

  • antibodies for cancer treatment
  • antibody–drug conjugate
  • antibody engineering
  • alternative antibody isotypes
  • bispecific antibodies
  • cancer therapy
  • combination therapies
  • immune cell engagers
  • immunomodulatory antibody
  • immunotherapy
  • targeted therapy

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

3 pages, 174 KiB  
Editorial
Targeted Immunotherapies for Cancers
by Anthony Cheung and Alicia Chenoweth
Cancers 2024, 16(1), 11; https://doi.org/10.3390/cancers16010011 - 19 Dec 2023
Viewed by 690
Abstract
Advancements in immunotherapy have revolutionized cancer treatment in a broad variety of hematological and solid malignancies and rejuvenated the field of cancer immunology [...] Full article
(This article belongs to the Special Issue Targeted Immunotherapies for Cancers)

Research

Jump to: Editorial, Review

19 pages, 1218 KiB  
Article
Phase 4 Multinational Multicenter Retrospective and Prospective Real-World Study of Nivolumab in Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck
by Anagha Gogate, Bryan Bennett, Zia Poonja, Grant Stewart, Ana Medina Colmenero, Petr Szturz, Courtney Carrington, Clara Castro, Eric Gemmen, Ashley Lau, Alberto Carral Maseda, Eric Winquist, Virginia Arrazubi, Desiree Hao, Audrey Cook, Joaquina Martinez Galan, Lisardo Ugidos, David Fernández Garay, David Gutierrez Abad and Robert Metcalf
Cancers 2023, 15(14), 3552; https://doi.org/10.3390/cancers15143552 - 9 Jul 2023
Cited by 2 | Viewed by 1528
Abstract
This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and [...] Read more.
This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively. Across both studies, the median age was 64.0 years, 80.9% were male, and 52.6% were former smokers. Clinical outcomes of interest included real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). The median rwOS was 9.2 months. Among patients with at least one assessment, 21.7% reported their best response as ‘partial response’, with 3.9% reporting ‘complete response’. The median duration of response (DoR) and median rwPFS were 11.0 months and 3.9 months, respectively. At baseline, VOLUME-PRO patients reported difficulties relating to fatigue, physical and sexual functioning, dyspnea, nausea, sticky saliva, dry mouth, pain/discomfort, mobility, and financial difficulties. There were improvements in social functioning and financial difficulties throughout the study; however, no other clinically meaningful changes were noted. No new safety concerns were identified. This real-world, multinational, multicenter, retrospective and prospective study supports the effectiveness and safety of nivolumab for R/M SCCHN patients. Full article
(This article belongs to the Special Issue Targeted Immunotherapies for Cancers)
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15 pages, 2584 KiB  
Article
A New Optimized Version of a Colorectal Cancer-Targeted Immunotoxin Based on a Non-Immunogenic Variant of the Ribotoxin α-Sarcin
by Javier Narbona, Rubén G. Gordo, Jaime Tomé-Amat and Javier Lacadena
Cancers 2023, 15(4), 1114; https://doi.org/10.3390/cancers15041114 - 9 Feb 2023
Cited by 2 | Viewed by 1611
Abstract
Due to its incidence and mortality, cancer remains one of the main risks to human health and lifespans. In order to overcome this worldwide disease, immunotherapy and the therapeutic use of immunotoxins have arisen as promising approaches. However, the immunogenicity of foreign proteins [...] Read more.
Due to its incidence and mortality, cancer remains one of the main risks to human health and lifespans. In order to overcome this worldwide disease, immunotherapy and the therapeutic use of immunotoxins have arisen as promising approaches. However, the immunogenicity of foreign proteins limits the dose of immunotoxins administered, thereby leading to a decrease in its therapeutic benefit. In this study, we designed two different variants of non-immunogenic immunotoxins (IMTXA33αSDI and IMTXA33furαSDI) based on a deimmunized variant of the ribotoxin α-sarcin. The inclusion of a furin cleavage site in IMTXA33furαSDI would allow a more efficient release of the toxic domain to the cytosol. Both immunotoxins were produced and purified in the yeast Pichia pastoris and later functionally characterized (both in vitro and in vivo), and immunogenicity assays were carried out. The results showed that both immunotoxins were functionally active and less immunogenic than the wild-type immunotoxin. In addition, IMTXA33furαSDI showed a more efficient antitumor effect (both in vitro and in vivo) due to the inclusion of the furin linker. These results constituted a step forward in the optimization of immunotoxins with low immunogenicity and enhanced antitumor activity, which can lead to potential better outcomes in cancer treatment. Full article
(This article belongs to the Special Issue Targeted Immunotherapies for Cancers)
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Graphical abstract

18 pages, 3373 KiB  
Article
Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells
by Osamu Sato, Takahiro Tsuchikawa, Takuma Kato, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Yuta Takeuchi, Katsunori Sasaki, Toru Nakamura, Kazufumi Umemoto, Tomohiro Suzuki, Linan Wang, Yizheng Wang, Kanako C. Hatanaka, Tomoko Mitsuhashi, Yutaka Hatanaka, Hiroshi Shiku and Satoshi Hirano
Cancers 2023, 15(3), 601; https://doi.org/10.3390/cancers15030601 - 18 Jan 2023
Cited by 4 | Viewed by 2592
Abstract
Chimeric antigen receptor engineered T cell (CAR-T) therapy has high therapeutic efficacy against blood cancers, but it has not shown satisfactory results in solid tumors. Therefore, we examined the therapeutic effect of CAR-T therapy targeting carcinoembryonic antigen (CEA) in pancreatic adenocarcinoma (PDAC). CEA [...] Read more.
Chimeric antigen receptor engineered T cell (CAR-T) therapy has high therapeutic efficacy against blood cancers, but it has not shown satisfactory results in solid tumors. Therefore, we examined the therapeutic effect of CAR-T therapy targeting carcinoembryonic antigen (CEA) in pancreatic adenocarcinoma (PDAC). CEA expression levels on the cell membranes of various PDAC cell lines were evaluated using flow cytometry and the cells were divided into high, medium, and low expression groups. The relationship between CEA expression level and the antitumor effect of anti-CEA-CAR-T was evaluated using a functional assay for various PDAC cell lines; a significant correlation was observed between CEA expression level and the antitumor effect. We created orthotopic PDAC xenograft mouse models and injected with anti-CEA-CAR-T; only the cell line with high CEA expression exhibited a significant therapeutic effect. Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy. Full article
(This article belongs to the Special Issue Targeted Immunotherapies for Cancers)
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21 pages, 3073 KiB  
Article
CDK Inhibition Primes for Anti-PD-L1 Treatment in Triple-Negative Breast Cancer Models
by Anthony Cheung, Alicia M. Chenoweth, Jelmar Quist, Heng Sheng Sow, Christina Malaktou, Riccardo Ferro, Ricarda M. Hoffmann, Gabriel Osborn, Eirini Sachouli, Elise French, Rebecca Marlow, Katie E. Lacy, Sophie Papa, Anita Grigoriadis and Sophia N. Karagiannis
Cancers 2022, 14(14), 3361; https://doi.org/10.3390/cancers14143361 - 11 Jul 2022
Cited by 7 | Viewed by 3188
Abstract
Triple-negative breast cancers (TNBC) expressing PD-L1 qualify for checkpoint inhibitor immunotherapy. Cyclin E/CDK2 is a potential target axis in TNBC; however, small-molecule drugs at efficacious doses may be associated with toxicity, and treatment alongside immunotherapy requires investigation. We evaluated CDK inhibition at suboptimal [...] Read more.
Triple-negative breast cancers (TNBC) expressing PD-L1 qualify for checkpoint inhibitor immunotherapy. Cyclin E/CDK2 is a potential target axis in TNBC; however, small-molecule drugs at efficacious doses may be associated with toxicity, and treatment alongside immunotherapy requires investigation. We evaluated CDK inhibition at suboptimal levels and its anti-tumor and immunomodulatory effects. Transcriptomic analyses of primary breast cancers confirmed higher cyclin E/CDK2 expression in TNBC compared with non-TNBC. Out of the three CDK2-targeting inhibitors tested, the CDK 2, 7 and 9 inhibitor SNS-032 was the most potent in reducing TNBC cell viability and exerted cytotoxicity against all eight TNBC cell lines evaluated in vitro. Suboptimal SNS-032 dosing elevated cell surface PD-L1 expression in surviving TNBC cells. In mice engrafted with human immune cells and challenged with human MDA-MB-231 TNBC xenografts in mammary fat pads, suboptimal SNS-032 dosing partially restricted tumor growth, enhanced the tumor infiltration of human CD45+ immune cells and elevated cell surface PD-L1 expression in surviving cancer cells. In tumor-bearing mice engrafted with human immune cells, the anti-PD-L1 antibody avelumab, given sequentially following suboptimal SNS-032 dosing, reduced tumor growth compared with SNS-032 alone or with avelumab without prior SNS-032 priming. CDK inhibition at suboptimal doses promotes immune cell recruitment to tumors, PD-L1 expression by surviving TNBC cells and may complement immunotherapy. Full article
(This article belongs to the Special Issue Targeted Immunotherapies for Cancers)
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Review

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17 pages, 675 KiB  
Review
A Panorama of Immune Fighters Armored with CARs in Acute Myeloid Leukemia
by Ilias Christodoulou and Elena E. Solomou
Cancers 2023, 15(11), 3054; https://doi.org/10.3390/cancers15113054 - 5 Jun 2023
Viewed by 2436
Abstract
Acute myeloid leukemia (AML) is a devastating disease. Intensive chemotherapy is the mainstay of treatment but results in debilitating toxicities. Moreover, many treated patients will eventually require hematopoietic stem cell transplantation (HSCT) for disease control, which is the only potentially curative but challenging [...] Read more.
Acute myeloid leukemia (AML) is a devastating disease. Intensive chemotherapy is the mainstay of treatment but results in debilitating toxicities. Moreover, many treated patients will eventually require hematopoietic stem cell transplantation (HSCT) for disease control, which is the only potentially curative but challenging option. Ultimately, a subset of patients will relapse or have refractory disease, posing a huge challenge to further therapeutic decisions. Targeted immunotherapies hold promise for relapsed/refractory (r/r) malignancies by directing the immune system against cancer. Chimeric antigen receptors (CARs) are important components of targeted immunotherapy. Indeed, CAR-T cells have achieved unprecedented success against r/r CD19+ malignancies. However, CAR-T cells have only achieved modest outcomes in clinical studies on r/r AML. Natural killer (NK) cells have innate anti-AML functionality and can be engineered with CARs to improve their antitumor response. CAR-NKs are associated with lower toxicities than CAR-T cells; however, their clinical efficacy against AML has not been extensively investigated. In this review, we cite the results from clinical studies of CAR-T cells in AML and describe their limitations and safety concerns. Moreover, we depict the clinical and preclinical landscape of CAR used in alternative immune cell platforms with a specific focus on CAR-NKs, providing insight into the future optimization of AML. Full article
(This article belongs to the Special Issue Targeted Immunotherapies for Cancers)
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26 pages, 1262 KiB  
Review
Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy
by Paola Muñoz-López, Rosa María Ribas-Aparicio, Elayne Irene Becerra-Báez, Karla Fraga-Pérez, Luis Fernando Flores-Martínez, Armando Alfredo Mateos-Chávez and Rosendo Luria-Pérez
Cancers 2022, 14(17), 4206; https://doi.org/10.3390/cancers14174206 - 30 Aug 2022
Cited by 25 | Viewed by 4982
Abstract
Cancer remains a public health problem worldwide. Although conventional therapies have led to some excellent outcomes, some patients fail to respond to treatment, they have few therapeutic alternatives and a poor survival prognosis. Several strategies have been proposed to overcome this issue. The [...] Read more.
Cancer remains a public health problem worldwide. Although conventional therapies have led to some excellent outcomes, some patients fail to respond to treatment, they have few therapeutic alternatives and a poor survival prognosis. Several strategies have been proposed to overcome this issue. The most recent approach is immunotherapy, particularly the use of recombinant antibodies and their derivatives, such as the single-chain fragment variable (scFv) containing the complete antigen-binding domains of a whole antibody that successfully targets tumor cells. This review describes the recent progress made with scFvs as a cancer diagnostic and therapeutic tool, with an emphasis on preclinical approaches and their potential use in clinical trials. Full article
(This article belongs to the Special Issue Targeted Immunotherapies for Cancers)
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