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Curated Papers > High-impact authoritative literature on "CAR-T therapy"

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer. ​

Literature Information ​

DOI10.3390/jcm9010182
PMID31936611
JournalJournal of clinical medicine
Impact Factor2.9
JCR QuartileQ1
Publication Year2020
Times Cited41
KeywordsChimeric antigen receptor (CAR)T-cell, colorectal cancer, immunotherapy, toxicity, trials
Literature TypeJournal Article, Review
ISSN2077-0383
Issue9(1)
AuthorsDaniel Sur, Andrei Havasi, Calin Cainap, Gabriel Samasca, Claudia Burz, Ovidiu Balacescu, Iulia Lupan, Diana Deleanu, AlexandruIrimie

TL;DR ​

This review examines the application of chimeric antigen receptor (CAR) T-cell therapy in colorectal cancer, highlighting its emergence as a promising immunotherapy following successful results in hematological malignancies. While the therapy shows modest benefits in treating solid tumors, challenges such as high costs, increased toxicities, relapses, and an unfavorable tumor microenvironment limit its effectiveness, warranting further research and development.

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Chimeric antigen receptor (CAR)T-cell · colorectal cancer · immunotherapy · toxicity · trials

Abstract ​

Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient's T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient's body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.

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Primary Questions Addressed ​

  1. What are the specific challenges faced by CAR T-cell therapy in treating solid tumors like colorectal cancer compared to hematological malignancies?
  2. How do the outcomes of CAR T-cell therapy in colorectal cancer compare with other immunotherapy approaches currently being tested?
  3. What advancements in CAR T-cell technology could potentially improve its efficacy and reduce toxicities in colorectal cancer patients?
  4. How does the tumor microenvironment in colorectal cancer affect the effectiveness of CAR T-cell therapy?
  5. What are the economic implications of CAR T-cell therapy for colorectal cancer, considering the high manufacturing and retail costs?

Key Findings ​

Research Background and Objectives ​

Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally, with limited survival rates for advanced stages. Despite advancements in chemotherapy and targeted therapies, treatment outcomes remain suboptimal, prompting interest in innovative approaches such as Chimeric Antigen Receptor (CAR) T-cell therapy. This review aims to summarize the current understanding, challenges, and future directions of CAR T-cell therapy in CRC.

Main Methods/Materials/Experimental Design ​

The review includes a comprehensive search of literature from PubMed, Web of Science, and clinicaltrials.gov, focusing on studies related to CAR T-cell therapy for CRC. A total of 22 relevant articles were analyzed based on specific inclusion criteria. The methodological framework for CAR T-cell therapy is illustrated below:

Mermaid diagram

Key Results and Findings ​

  1. Mechanism of Action: CAR T-cells are engineered to express receptors that target specific tumor antigens, enabling them to identify and destroy cancer cells.
  2. Clinical Trials: Initial trials have shown that CAR T-cell therapy can be safe and exhibit anti-tumor activity in CRC, but results are modest compared to hematological cancers.
  3. Toxicity and Side Effects: Common toxicities include cytokine release syndrome (CRS) and neurotoxicity, which can complicate treatment.
  4. Antigen Targeting: Potential targets for CAR T-cell therapy in CRC include carcinoembryonic antigen (CEA), guanylyl cyclase 2C (GUCY2C), and epithelial glycoprotein 40 (EGP40), among others.

Main Conclusions/Significance/Innovation ​

CAR T-cell therapy holds promise as a novel treatment modality for CRC, particularly with the right selection of antigens and combinatorial approaches. While initial findings are encouraging, the overall effectiveness remains limited in solid tumors compared to hematological malignancies. The review highlights the need for ongoing research to optimize CAR T-cell therapy for CRC, focusing on antigen selection and combination with other therapeutic strategies.

Research Limitations and Future Directions ​

  1. Limited Clinical Data: The scarcity of clinical data specifically addressing CAR T-cell therapy in CRC limits the understanding of its efficacy and safety.
  2. Challenges in Solid Tumors: The hostile tumor microenvironment and the presence of immunosuppressive factors complicate CAR T-cell effectiveness in solid tumors.
  3. Future Trials: There is a pressing need for more extensive clinical trials to explore different CAR designs, combination therapies, and optimal delivery methods to enhance treatment outcomes in CRC.

In summary, while CAR T-cell therapy presents a novel approach to CRC treatment, further research is essential to address current limitations and improve patient outcomes.

References ​

  1. Monoclonal antibody 3H11 chimeric antigen receptors enhance T cell effector function and exhibit efficacy against gastric cancer. - Haibo Han;Shanshan Wang;Ying Hu;Zhaowei Li;Wei Yang;Yunwei Lv;Limin Wang;Lianhai Zhang;Jiafu Ji - Oncology letters (2018)
  2. Anti-GPC3-CAR T Cells Suppress the Growth of Tumor Cells in Patient-Derived Xenografts of Hepatocellular Carcinoma. - Zhiwu Jiang;Xiaofeng Jiang;Suimin Chen;Yunxin Lai;Xinru Wei;Baiheng Li;Simiao Lin;Suna Wang;Qiting Wu;Qiubin Liang;Qifa Liu;Muyun Peng;Fenglei Yu;Jianyu Weng;Xin Du;Duanqing Pei;Pentao Liu;Yao Yao;Ping Xue;Peng Li - Frontiers in immunology (2016)
  3. Update in Systemic and Targeted Therapies in Gastrointestinal Oncology. - Nelson S Yee - Biomedicines (2018)
  4. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. - Kaichao Feng;Yelei Guo;Hanren Dai;Yao Wang;Xiang Li;Hejin Jia;Weidong Han - Science China. Life sciences (2016)
  5. Critical factors in chimeric antigen receptor-modified T-cell (CAR-T) therapy for solid tumors. - Lingli Yan;Bainan Liu - OncoTargets and therapy (2019)
  6. MicroRNA in colorectal cancer: new perspectives for diagnosis, prognosis and treatment. - Leonilde Bonfrate;Donato F Altomare;Maria Di Lena;Elisabetta Travaglio;Maria Teresa Rotelli;Angela De Luca;Piero Portincasa - Journal of gastrointestinal and liver diseases : JGLD (2013)
  7. Inactivation of Interferon Receptor Promotes the Establishment of Immune Privileged Tumor Microenvironment. - Kanstantsin V Katlinski;Jun Gui;Yuliya V Katlinskaya;Angelíca Ortiz;Riddhita Chakraborty;Sabyasachi Bhattacharya;Christopher J Carbone;Daniel P Beiting;Melanie A Girondo;Amy R Peck;Ellen Puré;Priya Chatterji;Anil K Rustgi;J Alan Diehl;Constantinos Koumenis;Hallgeir Rui;Serge Y Fuchs - Cancer cell (2017)
  8. Triplet (FOLFOXIRI) versus doublet (FOLFOX or FOLFIRI) backbone chemotherapy as first-line treatment of metastatic colorectal cancer: A systematic review and meta-analysis. - Rui Pedro Marques;Gonçalo S Duarte;Carmelo Sterrantino;Helena Luna Pais;António Quintela;Ana Paula Martins;João Costa - Critical reviews in oncology/hematology (2017)
  9. HER2 expression status in diverse cancers: review of results from 37,992 patients. - Min Yan;Maria Schwaederle;David Arguello;Sherri Z Millis;Zoran Gatalica;Razelle Kurzrock - Cancer metastasis reviews (2015)
  10. Multi Targeted CAR-T Cell Therapies for B-Cell Malignancies. - Nirav N Shah;Theresa Maatman;Parameswaran Hari;Bryon Johnson - Frontiers in oncology (2019)

Literatures Citing This Work ​

  1. Emerging Role of Immunotherapy for Colorectal Cancer with Liver Metastasis. - Xianzhe Yu;Lingling Zhu;Jiewei Liu;Ming Xie;Jiang Chen;Jianguo Li - OncoTargets and therapy (2020)
  2. Immune cell labelling and tracking: implications for adoptive cell transfer therapies. - Filippo Galli;Michela Varani;Chiara Lauri;Guido Gentiloni Silveri;Livia Onofrio;Alberto Signore - EJNMMI radiopharmacy and chemistry (2021)
  3. Stem cells as therapeutic targets in colorectal cancer. - Alicja Zalewski;Adam E Snook;Scott A Waldman - Personalized medicine (2021)
  4. Tumor regression and immunity in combination therapy with anti-CEA chimeric antigen receptor T cells and anti-CEA-IL2 immunocytokine. - Seung E Cha;Maciej Kujawski;Paul J Yazaki;Christine Brown;John E Shively - Oncoimmunology (2021)
  5. GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer. - Amanda N Lisby;John C Flickinger;Babar Bashir;Megan Weindorfer;Sanjna Shelukar;Madison Crutcher;Adam E Snook;Scott A Waldman - Expert review of precision medicine and drug development (2021)
  6. The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy. - Maurice Michel;Leonard Kaps;Annett Maderer;Peter R Galle;Markus Moehler - Cancers (2021)
  7. Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives. - Xuezhen Zeng;Simon E Ward;Jingying Zhou;Alfred S L Cheng - Cancers (2021)
  8. CAR-T cells: Early successes in blood cancer and challenges in solid tumors. - Hassan Dana;Ghanbar Mahmoodi Chalbatani;Seyed Amir Jalali;Hamid Reza Mirzaei;Stephan A Grupp;Eloah Rabello Suarez;Catarina Rapôso;Thomas J Webster - Acta pharmaceutica Sinica. B (2021)
  9. Cannabinoids, Medical Cannabis, and Colorectal Cancer Immunotherapy. - Mariia Zaiachuk;Nazar Pryimak;Olga Kovalchuk;Igor Kovalchuk - Frontiers in medicine (2021)
  10. A Mathematical Modeling Approach for Targeted Radionuclide and Chimeric Antigen Receptor T Cell Combination Therapy. - Vikram Adhikarla;Dennis Awuah;Alexander B Brummer;Enrico Caserta;Amrita Krishnan;Flavia Pichiorri;Megan Minnix;John E Shively;Jeffrey Y C Wong;Xiuli Wang;Russell C Rockne - Cancers (2021)

... (31 more literatures)

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