Related Experiment Video

Updated: Feb 12, 2026

Measuring Bone Remodeling and Recreating the Tumor-Bone Microenvironment Using Calvaria Co-culture and Histomorphometry
08:24

Measuring Bone Remodeling and Recreating the Tumor-Bone Microenvironment Using Calvaria Co-culture and Histomorphometry

Published on: March 14, 2020

7.3K

Avidity-optimized TCR-T cells target KRAS neoantigens for potent cancer clearance and tumor microenvironment

Zhaoduan Liang1,2,3, Fengqiong Guan3, Bingling Wu3

  • 1Bioland Laboratory, Guangzhou, Guangdong, China.

Frontiers in Immunology
|February 11, 2026
PubMed
Abstract

Insights

Researchers developed an improved T-cell receptor (TCR3) targeting KRAS neoantigens, demonstrating enhanced anti-tumor activity and immune cell recruitment. This KRAS-targeted immunotherapy shows promise for improving cancer treatment efficacy and safety.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • KRAS neoantigens are promising cancer targets, but current immunotherapies face efficacy and generalizability challenges.
  • No KRAS neoantigen-targeting immune products are currently approved for clinical use.

Purpose of the Study:

  • To develop and evaluate a novel T-cell receptor (TCR) mutant for enhanced KRAS neoantigen-targeted cancer immunotherapy.
  • To assess the efficacy, specificity, and tumor microenvironment interactions of the engineered TCR.

Main Methods:

  • Isolated a natural human T-cell receptor (TCR0) recognizing KRAS G12V neoantigens.
  • Engineered a mutant TCR (TCR3) to improve T-cell response and tumor cell killing.
  • Evaluated TCR3-T cell avidity, specificity, anti-tumor activity (in vitro and in vivo), and immune microenvironment modulation.

Main Results:

  • TCR3-T cells exhibited optimized avidity and potent anti-tumor responses against KRAS G12V-expressing tumor cell lines.
  • TCR3-T cells demonstrated specific killing of tumor cells, including those expressing PD-L1, with no observed toxicity to normal cells.
  • Engineered T cells showed resistance to immunosuppressive factors (IDO, TGF-β) and promoted immune cell infiltration via chemokines.

Conclusions:

  • The engineered TCR3 demonstrates significant potential for KRAS neoantigen-targeted immunotherapy.
  • TCR3 may overcome cancer immune escape mechanisms and enhance clinical effectiveness and safety.
  • Further development of TCR3 could lead to novel therapeutic strategies for KRAS-mutated cancers.
Keywords:
KRASTCR-T cellscancerneoantigenoptimized aviditytumor microenvironment

More Related Videos

Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion05:48

Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion

Published on: March 18, 2014

10.2K
A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies10:13

A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies

Published on: November 7, 2015

11.7K

Related Concept Videos

Affinity and Avidity01:41

Affinity and Avidity

Overview
39.2K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.9K
Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
11.3K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
6.0K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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...
9.0K
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
40.5K