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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

523
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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T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

721
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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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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Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

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Overview
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Related Experiment Video

Updated: Jun 29, 2025

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
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IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity.

Kelly D Moynihan1, Manu P Kumar1, Hussein Sultan2

  • 1Asher Biotherapeutics, Inc., South San Francisco, California.

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|April 2, 2024
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Targeting interleukin-2 (IL2) to CD8+ T cells enhances antitumor activity while reducing toxicity. This novel approach, exemplified by AB248, selectively expands CD8+ T cells, improving cancer therapy potential.

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Interleukin-2 (IL2) has pleiotropic effects on various cell types, impacting both anti-tumor activity and adverse effects like immunosuppression and toxicity.
  • Current IL2 therapies face challenges in maximizing therapeutic benefits while minimizing side effects due to its broad signaling.
  • Targeting IL2 specifically to CD8+ T cells, crucial for anti-tumor immunity, is a promising strategy to enhance the therapeutic index.

Purpose of the Study:

  • To investigate the potential of targeting IL2 to CD8+ T cells to improve its therapeutic efficacy and safety profile.
  • To develop and evaluate a novel CD8 cis-targeted IL2 agent, AB248, for enhanced anti-cancer activity.

Main Methods:

  • Development of AB248, a novel IL2 variant engineered for selective binding to CD8+ T cells.
  • In vitro assessment of AB248's effects on CD8+ T cells.
  • In vivo studies in non-human primates to evaluate selective CD8+ T cell expansion.
  • Preclinical efficacy and tolerability studies in mouse models using an AB248 surrogate compared to an untargeted IL2 agonist.

Main Results:

  • AB248 demonstrated over 500-fold preference for CD8+ T cells over natural killer cells and regulatory T cells (Tregs).
  • AB248 successfully recapitulated IL2's effects on CD8+ T cells in vitro and induced selective CD8+ T cell expansion in primates.
  • In mouse models, the AB248 surrogate showed superior anti-tumor activity and improved tolerability compared to non-targeted IL2.
  • Efficacy correlated with increased and phenotypically enhanced tumor-infiltrating CD8+ T cells, including a 'better effector' population.

Conclusions:

  • Targeting IL2 to CD8+ T cells can effectively decouple anti-tumor activity from toxicity.
  • AB248 represents a promising therapeutic strategy for cancer treatment by selectively engaging CD8+ T cells.
  • These preclinical findings support the clinical development of CD8+ T cell-selective IL2 agents for enhanced cancer immunotherapy.