Targeting Cancer: Microenvironment and Immunotherapy Innovations DOI Open Access
Irena Padzińska-Pruszyńska, Bartłomiej Taciak, Łukasz Kiraga

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13569 - 13569

Published: Dec. 18, 2024

In 2024, the United States was projected to experience 2 million new cancer diagnoses and approximately 611,720 cancer-related deaths, reflecting a broader global trend in which cases are anticipated exceed 35 by 2050. This increasing burden highlights ongoing challenges treatment despite significant advances that have reduced mortality 31% since 1991. Key obstacles include disease’s inherent heterogeneity complexity, such as resistance, stem cells, multifaceted tumor microenvironment (TME). The TME—comprising various immune blood vessels, biochemical factors—plays crucial role growth resistance therapies. Recent innovations treatment, particularly field of immuno-oncology, leveraged insights into TME interactions. An emerging example is FDA-approved therapy using tumor-infiltrating lymphocytes (TILs), demonstrating potential cell-based approaches solid tumors. However, TIL just one many strategies being explored. review provides comprehensive overview focusing on how novel therapies targeting or harnessing components could enhance efficacy address persistent care.

Language: Английский

Advancements in Melanoma Therapies: From Surgery to Immunotherapy DOI
Neda Shajari,

Behzad Baradaran,

Mohammad Reza Tohidkia

et al.

Current Treatment Options in Oncology, Journal Year: 2024, Volume and Issue: 25(8), P. 1073 - 1088

Published: July 27, 2024

Language: Английский

Citations

5
Cracking the Codes behind Cancer Cells’ Immune Evasion DOI Open Access
Nikita Mundhara, Pritam Sadhukhan

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8899 - 8899

Published: Aug. 15, 2024

Immune evasion is a key phenomenon in understanding tumor recurrence, metastasis, and other critical steps progression. The microenvironment (TME) constant flux due to the tumor's ability release signals that affect it, while immune cells within it can impact cancer cell behavior. Cancer undergo several changes, which change enrichment of different modulate activity existing microenvironment. evade surveillance by downregulating antigen presentation or expressing checkpoint molecules. High levels tumor-infiltrating lymphocytes (TILs) correlate with better outcomes, robust responses control growth. On contrary, increased Tregs, myeloid-derived suppressor cells, M2-like anti-inflammatory macrophages hinder effective predict poor prognosis. Overall, these mechanisms guides therapeutic strategies. Researchers aim TME enhance improve patient outcomes. In this review article, we strive summarize composition microenvironment, factors affecting (TIME), modalities targeting cells. This first-hand reference understand basics evasion.

Language: Английский

Citations

4
Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site DOI Creative Commons
María Paula Roberti, Pornpimol Charoentong,

Yanhong Lyu

et al.

OncoImmunology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Feb. 4, 2025

T cells that recognize tumor-specific mutations are crucial for cancer immunosurveillance and in adoptive transfer of TILs or transgenic-TCR cell products. However, their challenging identification isolation limits use clinical practice. Therefore, novel approaches to isolate needed. Here, we report the neoantigen-specific CD8+ from a vaccination site metastatic breast patient who received personalized vaccine. Based on somatic mutations, potential MHC binding epitopes were predicted, which 17 selected generate peptide Cutaneous biopsies processed after fifth cycle obtain infiltrating lymphocytes (VILs). IFNγ ELISpot revealed reactivity four peptides used Reactive VILs non-overlapping with those detected blood tumor-microenvironment. ScTCR Seq analysis presence clonotype further expanded round vitro stimulation validated be specific against private mutation, namely NCOR1L1475R, presented context HLA-B * 07:02, no wild-type peptide. Our study shows, first time, tumor mutation – generated at high frequencies can isolated standard methods TCR screening. The easy safe accessibility skin overcomes major hurdles current screening present exciting opportunities development innovative immunotherapeutic strategies.

Language: Английский

Citations

0
Infections in Patients with Solid Tumors Undergoing Adoptive Cellular Therapy DOI
Viswatej Avutu,

Jumanah N Algazaq,

Kenneth Seier

et al.

Transplantation and Cellular Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
T-cell receptors identified by a personalized antigen-agnostic screening approach target shared neoantigen KRAS Q61H DOI Creative Commons
Volker Lennerz,

Christoph Doppler,

Martina Fatho

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 17, 2025

Adoptive cell therapy (ACT) with TCR-engineered T-cells represents a promising alternative to TIL- or CAR-T therapies for patients advanced solid cancers. Currently, selection of therapeutic TCRs critically depends on knowing the target antigens, condition excluding most from treatment. Direct antigen-agnostic identification tumor-specific T-cell clonotypes and TCR-T manufacturing using their can advance ACT aggressive We present method identify surgical specimens by comparing TCRβ-chain repertoires TILs adjacent tissue-resident lymphocytes. In six out seven NSCLC-patients analyzed, our based TIL-abundance high tumor-to-nontumor frequency ratios was confirmed gene expression signatures determined scRNA-Seq. three patients, we demonstrated that predicted reacted against autologous tumors. For one these engineered cells four candidate showed reactivity patient's tumor HLA-matched NSCLC lines. The were then used screen neoantigens aberrantly expressed antigens. Three recognized recurrent driver-mutation KRAS Q61H-peptide ILDTAGHEEY presented HLA-A*01:01. also dominant in relapse, found free DNA. finding homologous independent Q61H-positive cancers suggests opportunity Q61H-expressing

Language: Английский

Citations

0
A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2024 DOI Creative Commons
Zinnet Şevval Aksoyalp, Gizem Kaykı-Mutlu,

Leszek Wojnowski

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Abstract The US Food and Drug Administration approved 50 new drugs nine cellular gene therapy products in 2024, i.e., a total of 59 medical therapies. latter group represented three treatments each for oncology hematology/immunotherapy, one neurology, genetic disorders, cardiovascular disorders. Oncology, neurological disorders (14, six, seven, respectively) also were highly prevalent among classic medications. Looking at trends over the past 5 years, we observe greater share first-in-class medications, more fast-track approvals, mRNA/gene/cell-based While small molecules remain largest fraction, their percentage has been declining substantially years. Taking together, these findings testify to commitment pharmaceutical industry innovative treatments, including conditions which no therapies existed. On other hand, there is trend approvals narrowly focused such as tumors defined by alterations.

Language: Английский

Citations

0
Ecological and evolutionary dynamics to design and improve ovarian cancer treatment DOI Creative Commons
Grace Han, Monica Alexander,

Julia Gattozzi

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(9)

Published: Aug. 29, 2024

Ovarian cancer ecosystems are exceedingly complex, consisting of a high heterogeneity cells. Development drugs such as poly ADP-ribose polymerase (PARP) inhibitors, targeted therapies and immunotherapies offer more options for sequential or combined treatments. Nevertheless, mortality in metastatic ovarian patients remains because cells consistently develop resistance to single combination therapies, urging need treatment designs that target the evolvability The evolutionary dynamics lead emerge from complex tumour microenvironment, heterogeneous populations, individual cell's plasticity. We propose successful management requires consideration ecological disease. Here, we review current challenges discuss principles evolution. conclude by proposing evolutionarily designed strategies cancer, with goal integrating longitudinal, quantitative data improve design drug resistance. KEY POINTS/HIGHLIGHTS: Tumours which non-cancer interact evolve dynamic ways. Conventional inevitably development they fail consider tumours' cellular Eco-evolutionarily should cell plasticity patient-specific characteristics clinical outcome prevent relapse.

Language: Английский

Citations

3
Clinical-scale, modular manufacturing of tumor-reactive TILs using a closed and automated culture system DOI Creative Commons

Christina Völzke,

Lisa Ehrhardt,

Laura Fischer

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 9, 2024

Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, translation TIL therapy for patients is still hampered by non-standardized laborious manufacturing procedures that are expensive produce highly variable cellular products. To address these limitations, CliniMACS Prodigy

Language: Английский

Citations

1
Tumor infiltrating lymphocytes (TILs) – pathologia, quo vadis? - A global survey DOI Creative Commons

Kristijan Skok,

Konstantin Bräutigam

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 266, P. 155775 - 155775

Published: Dec. 13, 2024

Language: Английский

Citations

1
Pre-Clinical Models for CAR T-Cell Therapy for Glioma DOI Creative Commons
Gust Vandecandelaere, Rishab Ramapriyan,

Matthew A. Gaffey

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1480 - 1480

Published: Sept. 4, 2024

Immunotherapy represents a transformative shift in cancer treatment. Among myriad immune-based approaches, chimeric antigen receptor (CAR) T-cell therapy has shown promising results treating hematological malignancies. Despite aggressive treatment options, the prognosis for patients with malignant brain tumors remains poor. Research leveraging CAR surged recent years. Pre-clinical models are crucial evaluating safety and efficacy of these therapies before they advance to clinical trials. However, current recapitulate human tumor environment varying degrees. Novel vitro vivo techniques offer opportunity validate but also have limitations. By strengths weaknesses various pre-clinical glioma models, this review aims provide roadmap development testing tumors.

Language: Английский

Citations

0