Targeting MICA with therapeutic antibodies for the treatment of cancer

Bonnafous, Cécile; Péri, Valentine; Trichard, Sylvia; Perrot, Ivan; Cornen, Stéphanie; Thielens, Ariane; Breso, Violette; Morel, Yannis; Rossi, Benjamín; Paturel, Carine; Gauthier, Laurent; Bléry, Mathieu

doi:10.1186/2051-1426-1-s1-p41

Cited by 4 publications

(5 citation statements)

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“…IPH43 (developed by Innate Pharma) is a MICA-specific antibody that binds to nearly all polymorphic classes of MICA. This antibody neutralizes soluble MICA, blocks the interaction of MICA with NKG2D and may also directly induce ADCC and complement-dependent cytotoxicity-mediated killing of MICA-expressing tumour cells 149 . Multiple clinical trials of IPH43 are underway.…”

Section: Killer Inhibitory Receptorsmentioning

confidence: 99%

Combination cancer immunotherapy and new immunomodulatory targets

Mahoney

Rennert²,

Freeman

2015

Nat Rev Drug Discov

1,125

907

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Targeting immune checkpoints such as programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has achieved noteworthy benefit in multiple cancers by blocking immunoinhibitory signals and enabling patients to produce an effective antitumour response. Inhibitors of CTLA4, PD1 or PDL1 administered as single agents have resulted in durable tumour regression in some patients, and combinations of PD1 and CTLA4 inhibitors may enhance antitumour benefit. Numerous additional immunomodulatory pathways as well as inhibitory factors expressed or secreted by myeloid and stromal cells in the tumour microenvironment are potential targets for synergizing with immune checkpoint blockade. Given the breadth of potential targets in the immune system, critical questions to address include which combinations should move forward in development and which patients will benefit from these treatments. This Review discusses the leading drug targets that are expressed on tumour cells and in the tumour microenvironment that allow enhancement of the antitumour immune response.

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Section: Killer Inhibitory Receptorsmentioning

confidence: 99%

Combination cancer immunotherapy and new immunomodulatory targets

Mahoney

Rennert²,

Freeman

2015

Nat Rev Drug Discov

1,125

907

View full text Add to dashboard Cite

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“…For SCLC-P and SCLC-I, we identified MICA, the gene which encodes MHC class I polypeptide-related sequence A, as highly expressed (Figures S5M-S5O). MICA is the target of a molecule (IPH43) currently in preclinical development (Bonnafous et al, 2013). Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), is the target of labetuzumab govitecan, an ADC in clinical investigation for patients with refractory metastatic colorectal cancer, as well as a CAR T cell (Das, 2017;Dotan et al, 2017;Sharkey et al, 2018;Thistlethwaite et al, 2017).…”

Section: Unique Therapeutic Vulnerabilities Across Subtypesmentioning

confidence: 99%

Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

et al. 2021

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“…4 D). Human NKG2D ligands consist of the ULBP family, including ULBP1-6, MIC-A, and MIC-B [ 6 ] [ 35 ]. Of note, a more-than-twofold increase in the expression of ULBP2, ULBP5, and ULBP6 was observed, whereas the expression of ULBP1 and ULBP3 decreased.…”

Section: Resultsmentioning

confidence: 99%

“…Fig 6. Immunogenic senescence improves LUNX-targeting therapy in a model of lung cancer (A-C) Mitoxantrone treatment improved LUNX expression in vivo.…”

mentioning

confidence: 99%

Immunogenic senescence sensitizes lung cancer to LUNX-targeting therapy

Jiao

Zheng

et al. 2021

Cancer Immunol Immunother

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The higher immunogenicity of tumors usually predicts favorable therapeutic responses. Tumor antigens dominate the immunogenic character within tumors. We investigated if there was a targetable tumor antigen during immunogenic chemotherapy within lung cancer. Chemotherapy-induced immunogenic senescence was demonstrated using a multi-marker, three-step workflow, and RNA-sequencing data. The ability of anti-lung-specific X protein (LUNX) antibody to suppress the survival of senescent lung cancer cells was evaluated in vitro and in vivo using real-time cytotoxicity analysis and xenograft mouse models, respectively. The induction of cellular senescence by immunogenic chemotherapy boosted cell-surface shuttling of LUNX and enhanced the immunogenic features of senescent tumor cells, which sensitized lung cancer cells to anti-LUNX antibody-mediated therapy and contributed to tumor suppression. The immunogenic senescence-mediated anti-tumor response was triggered by the direct action of antibody on tumor cells, strengthened by natural-killer cells through an antibody-dependent cell-mediated cytotoxicity response, and ultimately, led to tumor control. Our findings suggest that LUNX is a lung cancer targetable-immunogenic antigen. The proportion of lung cancers responding to LUNX-targeting therapy could be expanded substantially by immunogenic chemotherapy that induces senescence-associated translocation of LUNX to the plasma membrane.

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Targeting MICA with therapeutic antibodies for the treatment of cancer

Cited by 4 publications

References 0 publications

Combination cancer immunotherapy and new immunomodulatory targets

Combination cancer immunotherapy and new immunomodulatory targets

Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

Immunogenic senescence sensitizes lung cancer to LUNX-targeting therapy

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