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  • Table Ronde LyonBioPôle

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    Erwan
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    1) Only 12.5% of cancer patients benefit from immunotherapy treatment with immune checkpoint blockade (ICB). 2) ICBs require a pre-existing immune response against the tumor for effectiveness, but many tumors are able to inhibit immune responses. 3) Caloric restriction mimetics (CRMs) have been shown to synergize with chemotherapy in a CD8-dependent manner, inducing an immune response by depleting regulatory T-cells in the tumor bed. 4) In a model of a chemotherapy and ICB-resistant tumor, the addition of CRM019 to chemotherapy and ICB induced a complete response, demonstrating the potential for CRMs to improve ICB effectiveness.

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    Table ronde LyonBiopôle

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    211011 Table Ronde LyonBioPôle

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    1) Only 12.5% of cancer patients benefit from immunotherapy treatment with immune checkpoint blockade (ICB). 2) ICBs require a pre-existing immune response against the tumor for effectiveness, but many tumors are able to inhibit immune responses. 3) Caloric restriction mimetics (CRMs) have been shown to synergize with chemotherapy in a CD8-dependent manner, inducing an immune response by depleting regulatory T-cells in the tumor bed. 4) In a model of a chemotherapy and ICB-resistant tumor, the addition of CRM019 to chemotherapy and ICB induced a complete response, demonstrating the potential for CRMs to improve ICB effectiveness.

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    17 views6 pages

    Table Ronde LyonBioPôle

    Uploaded by

    Erwan
    1) Only 12.5% of cancer patients benefit from immunotherapy treatment with immune checkpoint blockade (ICB). 2) ICBs require a pre-existing immune response against the tumor for effectiveness, but many tumors are able to inhibit immune responses. 3) Caloric restriction mimetics (CRMs) have been shown to synergize with chemotherapy in a CD8-dependent manner, inducing an immune response by depleting regulatory T-cells in the tumor bed. 4) In a model of a chemotherapy and ICB-resistant tumor, the addition of CRM019 to chemotherapy and ICB induced a complete response, demonstrating the potential for CRMs to improve ICB effectiveness.

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    of 6

    Table Ronde LBP

    2021-10-11
    Immunotherapy: a revolution for the 12,5%
    Immune Checkpoint Blockade (ICB) Yet only 12,46% of patients benefit
    is a revolution in cancer treatment from ICB treatment

    US 2018 ICB response rates


    100%

    Responding
    90%

    Eligible
    80%

    1st Challenge
    70%

    2nd Challenge
    60%

    50%

    Non Responding
    40%

    Non Eligible
    30%

    20%

    10%

    0%
    Cancer Patients Eligible Cancer Patients
    Pooled, pan-cancer, pan-ICB data from Haslam & Prasad, JAMA Netw Open. 2019
    Confidential - do not distribute 2
    ICBs need an immune response
    ICB lifts tumor-led inhibition of anti- Consequence: need for a pre-
    cancer immune response existing immune response

    Lymphocyte Lymphocyte

    PD1
    ICB
    ? PD1

    Tumor cell Tumor cell Tumor cell Tumor cell

    Confidential - do not distribute 3


    CRMs induce an immune response
    Caloric Restriction Mimetics (CRM) This effect is mediated by regulatory
    synergize with chemotherapy in a CD8-
    dependent fashion T-cell depletion in the tumor bed

    ⚫ PBS ◆ CRM + MTX


    ◼ MTX ◆ CRM + MTX + αCD4
    ◆ CRM ⚫ CRM + MTX + αCD8 PBS | CRM | MTX | CRM +
    MTX

    Confidential - do not distribute 4


    Proof of concept Chemo +
    Ctrl
    CRM019
    CRM019 induces complete
    ICB response in an ICB- Chemo Chemo
    + ICB
    resistant model

    Tumor volume (mm3)


    Syngeneic immunocompetent model, strain
    MCA 205 (resistant against immunotherapies), Triple combination
    chemotherapy : mitoxantrone, ICB: anti PD1,
    n>8/group Chemo + ICB +
    CRM019
    p<0,001

    CRM + ICI
    Chimio Patented 2018
    Time (days)

    Confidential - do not distribute 5


    Thank you!
    Erwan ERIAU
    erwan@eriau.eu
    (+33) (0)6 74 32 76 90

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