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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Cancer Vaccines01:30

Cancer Vaccines

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Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
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Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

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Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
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  1. Home
  2. Research Domains
  3. Biomedical And Clinical Sciences
  4. Oncology And Carcinogenesis
  5. Predictive And Prognostic Markers
  6. Novel Immunotherapeutics Against Lgr5 To Target Multiple Cancer Types.
  1. Home
  2. Research Domains
  3. Biomedical And Clinical Sciences
  4. Oncology And Carcinogenesis
  5. Predictive And Prognostic Markers
  6. Novel Immunotherapeutics Against Lgr5 To Target Multiple Cancer Types.

Related Experiment Video

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
07:55

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer

Published on: January 17, 2025

686

Novel immunotherapeutics against LGR5 to target multiple cancer types.

Hung-Chang Chen1,2, Nico Mueller1, Katherine Stott3

  • 1University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.

EMBO Molecular Medicine
|August 21, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

A novel antibody targeting Leucine-rich repeat-containing G-protein coupled Receptor 5 (LGR5) shows promise. This antibody, α-LGR5, effectively targets various cancers and serves as a foundation for developing potent immunotherapies.

Keywords:
ADCBiTECARCancer Immunotherapeutics

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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

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Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Leucine-rich repeat-containing G-protein coupled Receptor 5 (LGR5) is overexpressed in several aggressive cancers, including colorectal cancer (CRC), hepatocellular carcinoma (HCC), and pre-B acute lymphoblastic leukemia (pre-B-ALL).
  • Targeting LGR5 presents a potential therapeutic strategy for these malignancies.

Purpose of the Study:

  • To develop and validate a specific antibody against the extracellular domain of human LGR5 (α-LGR5).
  • To evaluate the therapeutic potential of α-LGR5 in various formats, including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cells, for targeting LGR5-expressing cancers.

Main Methods:

  • Development and validation of a specific antibody (α-LGR5) targeting human LGR5.
  • Generation of α-LGR5-based immunotherapeutic modalities: antibody-drug conjugate (α-LGR5-ADC), bispecific T-cell engager (α-LGR5-BiTE), and chimeric antigen receptor (α-LGR5-CAR) T-cells.
LGR5
  • In vitro and in vivo efficacy studies using cancer cell lines and a murine model of human pre-B-ALL.
  • Main Results:

    • α-LGR5 detected LGR5 overexpression in over 90% of CRC, HCC, and pre-B-ALL tumor cells.
    • α-LGR5-ADC demonstrated potent in vitro and in vivo anti-tumor efficacy in a pre-B-ALL murine model, reducing tumor burden significantly.
    • α-LGR5-BiTE and α-LGR5-CAR T-cells also showed specific cancer cell killing and reduced tumor burden in vivo.

    Conclusions:

    • α-LGR5 is a versatile antibody that can be utilized as a research tool, biomarker, and a foundational component for developing novel immunotherapies.
    • The developed α-LGR5-based therapeutics offer a promising portfolio for targeting a wide range of LGR5-expressing cancers.