Advances in antibody-based therapy in oncology

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(2), P. 165 - 180

Published: Feb. 20, 2023

Language: Английский

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Research progress on dendritic cell vaccines in cancer immunotherapy

Experimental Hematology and Oncology, Journal Year: 2022, Volume and Issue: 11(1)

Published: Jan. 24, 2022

Dendritic cell (DC) vaccines induce specific immune responses that can selectively eliminate target cells. In recent years, many studies have been conducted to explore DC vaccination in the treatment of hematological malignancies, including acute myeloid leukemia and myelodysplastic syndromes, as well other nonleukemia malignancies. There are at least two different strategies use DCs promote antitumor immunity: situ canonical vaccination. Monocyte-derived (mo-DCs) leukemia-derived (DCleu) main types used for AML MDS thus far. Different cancer-related molecules such peptides, recombinant proteins, apoptotic leukemic cells, whole tumor cells or lysates DCs/DCleu containing a vaster antigenic repertoire with RNA electroporation, antigen sources load DCs. To enhance vaccine efficacy, new strategies, combination conventional chemotherapy, monospecific/bispecific antibodies checkpoint-targeting therapies, explored. After decade trials tribulations, much progress has made promise emerged field. this review we summarize advances immunotherapy AML/MDS

Language: Английский

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A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies

Stem Cell Research & Therapy, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 28, 2021

Abstract To date, two chimeric antigen receptors (CAR)-T cell products from autologous T cells have been approved by The United States Food and Drug Administration (FDA). case-by-case generation setting is largely considered as a pivotal restraining cause for its large-scale clinical use because of the costly prolonged manufacturing procedure. Further, activated CAR-T mainly express immune checkpoint molecules, including CTLA4, PD1, LAG3, abrogating anti-tumor activity. In addition, therapy potently results in some toxicity, such cytokine releases syndrome (CRS). Therefore, development universal allogeneic with higher effects paramount importance. Thus, genome-editing technologies, particular, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 are currently being used to establish “off-the-shelf” robust resistance cell-suppressive molecules. fact, that simultaneous ablation PD-1, receptor alpha constant (TRAC or TCR), also β-2 microglobulin (B2M) CRISPR-Cas9 technique can support manufacture PD-L1. . Indeed, β2M TARC severely hinder swift elimination those foreign HLA-I thereby enables healthy donors persistence vivo. Herein, we will deliver brief overview application context tumor immunotherapy. More importantly, discuss recent finding concerning genome editing technologies preparing effectively counter escape, special focus on technology.

Language: Английский

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Cancer treatments: Past, present, and future

Cancer Genetics, Journal Year: 2024, Volume and Issue: 286-287, P. 18 - 24

Published: June 17, 2024

Language: Английский

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Targeting macrophages in hematological malignancies: recent advances and future directions

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Aug. 17, 2022

Abstract Emerging evidence indicates that the detection and clearance of cancer cells via phagocytosis induced by innate immune checkpoints play significant roles in tumor-mediated escape. The most well-described are “don’t eat me” signals, including CD47/signal regulatory protein α axis (SIRPα), PD-1/PD-L1 axis, CD24/SIGLEC-10 MHC-I/LILRB1 axis. Molecules have been developed to block these pathways enhance phagocytic activity against tumors. Several clinical studies investigated safety efficacy CD47 blockades, either alone or combination with existing therapy hematological malignancies, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), lymphoma. However, only a minority patients responses treatments alone. Combining blockades other treatment modalities studies, early results suggesting synergistic therapeutic effect. Targeting macrophages bispecific antibodies being explored blood therapy. Furthermore, reprogramming pro-tumor anti-tumor macrophages, CAR (CAR-M) demonstrate activities. In this review, we elucidated distinct types macrophage-targeted strategies from preclinical experiments trials, outlined potential approaches developed.

Language: Английский

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Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 24, 2023

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), Notch inhibitory ligand, attractive therapeutic target because it overexpressed on the surface of SCLC cells minimal expression normal cells. Several DLL3-targeted being developed for and other carcinomas, including antibody-drug conjugates (ADCs), T-cell engager (TCE) molecules, chimeric antigen receptor (CAR) therapies. First, we discuss clinical experience rovalpituzumab tesirine (Rova-T), DLL3-targeting ADC, development which was halted due lack efficacy phase studies, view understanding lessons that can be garnered rapidly evolving landscape SCLC. We then review preclinical data several agents currently development, TCE molecules-tarlatamab (formerly known AMG 757), BI 764532, HPN328-and CAR therapy 119. conclude discussion future challenges opportunities therapies, utility DLL3 biomarker patient selection progression, potential rational combinatorial approaches enhance efficacy.

Language: Английский

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Immunotherapy in hematologic malignancies: achievements, challenges and future prospects

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 18, 2023

Abstract The immune-cell origin of hematologic malignancies provides a unique avenue for the understanding both mechanisms immune responsiveness and escape, which has accelerated progress immunotherapy. Several categories immunotherapies have been developed are being further evaluated in clinical trials treatment blood cancers, including stem cell transplantation, checkpoint inhibitors, antigen-targeted antibodies, antibody-drug conjugates, tumor vaccines, adoptive therapies. These shown potential to induce long-term remission refractory or relapsed patients led paradigm shift cancer with great success. Different immunotherapeutic approaches their advantages but also shortcomings that need be addressed. To provide clinicians timely information on these revolutionary therapeutic approaches, comprehensive review historical perspectives applications considerations Here, we first outline recent advances made various malignancies. We discuss specific action, summarize outcomes malignancies, as well adverse effects toxicity management then novel insights into challenges future directions.

Language: Английский

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Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: July 27, 2023

Abstract Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and another directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells CD16a NK cells. The first engager (the anti-CD19 blinatumomab) was approved by the FDA 2014, but no other hit market until 2022. Now field is gaining momentum, three approvals 2022 2023 (as May): anti-CD20 × anti-CD3 mosunetuzumab epcoritamab anti-B maturation (BCMA) teclistamab, molecules regulatory review. will likely revolutionize treatment hematological malignancies short term, as they considerably more potent than conventional monoclonal recognizing same tumor antigens. thriving, plethora different formats targets, around 100 bispecific already clinical trials. Bispecific also early-stage studies may offer similar efficacy milder side effects. Trispecific (engaging either or receptors) raise game even further third moiety, which allows targeting additional to increase specificity avoid escape costimulatory receptors on improve its functions. Altogether, these change paradigm relapsed refractory malignancies.

Language: Английский

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Cytokine release syndrome and cancer immunotherapies – historical challenges and promising futures

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 25, 2023

Cancer is the leading cause of death worldwide. immunotherapy involves reinvigorating patient's own immune system to fight against cancer. While novel approaches like Chimeric Antigen Receptor (CAR) T cells, bispecific cell engagers, and checkpoint inhibitors have shown promising efficacy, Cytokine Release Syndrome (CRS) a serious adverse effect remains major concern. CRS phenomenon hyperactivation that results in excessive cytokine secretion, if left unchecked, it may lead multi-organ failure death. Here we review pathophysiology CRS, its occurrence management context cancer immunotherapy, screening can be used assess de-risk drug discovery earlier clinical setting with more predictive pre-clinical data. Furthermore, also sheds light on potential immunotherapeutic overcome associated activation.

Language: Английский

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Revolutionizing cancer treatment: comprehensive insights into immunotherapeutic strategies

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(2)

Published: Jan. 9, 2024

Language: Английский

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