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Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures
- Two types of functional IL-2Rs
- IL-2 complexed to IL-2R
- Model of IL-2R signal transduction
- Model of IL-2 function 1980s
- IL-2 is more than a T cell growth factor
- IL-2 has a key role in the production of regulatory T cells
- Low IL-2 signalling supports homeostasis of T regulatory cells
- Essential roles for IL-2 in the immune system
- Treg and Teff cells and their dependency on IL-2
- Expression of CD25 explains the differential sensitivity of cells to IL-2
- Low-dose IL-2 optimally activates STAT5 and gene expression in human Tregs
- Does treatment of autoimmune patients with low-dose recombinant IL-2 selectively boost Tregs and leads to clinical benefit?
- Therapy for autoimmune diseases
- Rationale of low-dose IL-2 as a therapy for autoimmunity
- Past and ongoing clinical testing with low-dose IL-2
- Clinical testing of low-dose IL-2 as a monotherapy
- IL-2 is not an ideal biologic for IL-2-based therapy
- Strategies to improve the selectivity, pharmacokinetics, and pharmacodynamics of IL-2
- Design of the mouse IL-2/CD25 fusion protein
- Outcomes of fusing IL-2 to CD25
- Transdimer mIL-2/CD25 slowly releases IL-2 to persistently stimulate the high affinity IL-2R
- mIL-2/CD25 leads to extended IL-2R signaling and gene activation to support Treg proliferation
- Inhibition of lupus by mIL-2/CD25 in NZB × NZW mice
- Low-dose mIL-2/CD25 controls diabetes in NOD mice
- Consequences of mIL-2/CD25 on autoimmune diabetes in NOD mice
- Key properties of IL-2/CD25
- Can the immune activating properties of IL-2 be harnessed for cancer immunotherapy?
- IL-2 as a cancer immunotherapy
- Limits of IL-2 immunotherapy of cancer
- Current favored approach for IL-2-dependent anti-tumor immunity
- Potential advantages and limitations of high-dose IL-2/CD25 for use in cancer immunotherapy
- Questions
- High-dose mIL-2/CD25 elicits potent antitumor responses in immunogenic tumors
- Intermediate-affinity IL-2R-targeted therapy is not more effective than IL-2/CD25
- PD-1 blockade augments the antitumor activity of high-dose mIL-2/CD25
- Consequences of high-dose mIL-2/CD25 in anti-tumor responses
- Clinical Implications
Topics Covered
- IL-2Rs
- IL-2 and regulatory T cells
- Therapy for autoimmune diseases
- Low-dose IL-2
- Clinical testing
- IL-2 for autoimmunity and cancer
- Mouse IL-2/CD25 fusion protein
- Key properties of IL-2/CD25
- IL-2 as a cancer immunotherapy
- IL-2-dependent anti-tumor immunity
- High-dose IL-2/CD25
- Clinical implications
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Malek, T. (2023, October 31). IL-2 in the immunotherapy of autoimmunity and cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 11, 2024, from https://doi.org/10.69645/VLUZ3720.Export Citation (RIS)
Publication History
Financial Disclosures
- Thomas Malek and the University of Miami have a sponsored research and exclusive licensing agreements with Bristol Myers Squibb related to IL-2/CD25 fusion proteins and its related patent (WO2016022671A1). Thomas Malek and the University of Miami receive royalties for its commercialization.
Other Talks in the Series: The Immune System - Key Concepts and Questions
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, I'm Tom Malek.
I'm professor and chair in
the Department of
Microbiology and Immunology
at the University of Miami,
Miller School of Medicine.
Today I'm going to discuss
with you the current use of
IL-2 in the immunotherapy
of autoimmunity and cancer.
I'm going to divide this
lecture into three parts.
First, give some background
on the IL-2 receptor system.
Then I'll move to talking about
IL-2 and therapy for
autoimmune diseases and
also discuss a new IL-2 biologic
that my lab has developed.
Then finally discuss how
IL-2 is being used for
the therapy of cancer.
0:46
Before I begin, I
need to disclose that
I and the University of Miami
have a sponsored research,
an exclusive licensing
agreement with
Bristol Meyers Squibb related to
this IL-2/CD25 fusion protein,
which I'll talk more
about later in the talk.
1:05
But as a start, I'd
like to give some
of the basics of the
IL-2 receptor system.
First to discuss what type
of IL-2 receptors are there.
There's two major forms,
an intermediate
affinity IL-2 receptor
and the high affinity
IL-2 receptor.
These two types of
receptors differ based on
their sub unit composition.
The intermediate
affinity has two chains,
IL-2 receptor, Beta and Gamma,
or as shown on the slide,
CD122 and CD132,
and these are found primarily on
CD8 memory T cells and
natural killer cells.
The high affinity receptor
includes CD122 and CD
132 but also the IL-2
receptor alpha chain or CD25.
This receptor is found on CD4
and CD8 T effector cells,
on regulatory T cells and
ILC2s in a small
subset of NK cells.
Now an important difference
between the two is that
much lower amount of IL-2 is
necessary to trigger the
high affinity receptor,
approximately 100 fold less, so
cells that express the high
affinity receptor will
be able to respond in
environments of low IL-2.