Novel strategies exploiting interleukin-12 in cancer immunotherapy

Cirella, Assunta; Luri-Rey, Carlos; Trani, Claudia Augusta Di; Teijeira, Álvaro; Olivera, Irene; Bolaños, Elixabet; Castañón, Eduardo; Palencia, Belén; Brocco, Davide; Fernandez‐Sendin, Myriam; Aranda, Fernando; Berraondo, Pedro; Melero, Ignacio

doi:10.1016/j.pharmthera.2022.108189

Cited by 72 publications

(53 citation statements)

References 132 publications

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“…This approach is attractive especially with recent advances in novel gene delivery platforms of IL12 like plasmids, mRNA based or viral vectors. 42 , 43 …”

Section: Discussionmentioning

confidence: 99%

Immunotherapy with IL12 and PD1/CTLA4 inhibition is effective in advanced ovarian cancer and associates with reversal of myeloid cell-induced immunosuppression

et al. 2023

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The tumor microenvironment (TME) in ovarian cancer (OC) is characterized by immune suppression, due to an abundance of suppressive immune cells populations. To effectively enhance the activity of immune checkpoint inhibition (ICI), there is a need to identify agents that target these immunosuppressive networks while promoting the recruitment of effector T cells into the TME. To this end, we sought to investigate the effect of the immunomodulatory cytokine IL12 alone or in combination with dual-ICI (anti-PD1 + anti-CTLA4) on anti-tumor activity and survival, using the immunocompetent ID8-VEGF murine OC model. Detailed immunophenotyping of peripheral blood, ascites, and tumors revealed that durable treatment responses were associated with reversal of myeloid cell-induced immune suppression, which resulted in enhanced anti-tumor activity by T cells. Single cell transcriptomic analysis further demonstrated striking differences in the phenotype of myeloid cells from mice treated with IL12 in combination with dual-ICI. We also identified marked differences in treated mice that were in remission compared to those whose tumors progressed, further confirming a pivotal role for the modulation of myeloid cell function to allow for response to immunotherapy. These findings provide the scientific basis for the combination of IL12 and ICI to improve clinical response in OC.

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“…This approach is attractive especially with recent advances in novel gene delivery platforms of IL12 like plasmids, mRNA based or viral vectors. 42 , 43 …”

Section: Discussionmentioning

confidence: 99%

Immunotherapy with IL12 and PD1/CTLA4 inhibition is effective in advanced ovarian cancer and associates with reversal of myeloid cell-induced immunosuppression

et al. 2023

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“…They can regulate immune proliferation, differentiation, and effector function, and are crucial for immune cells to fight against tumor cells [73]. IL-12, a heterodimeric cytokine, can promote the repolarization of macrophages from the M2 to M1 phenotype and thus enhance anti-tumor immune responses [74]. To this end, He et al [75] developed polypeptide/hyaluronic acid (HA)/protamine/calcium carbonate (CaCO 3 )/DNA nanoparticles (PHNPs) to deliver IL-12 gene-encoding pDNA (pDNA IL-12) into TAMs and cancer cells.…”

Section: Gene Therapy Targeting Tams For Cancer Treatmentmentioning

confidence: 99%

Macrophages as potential targets in gene therapy for cancer treatment

Huang

Wang

Gong

et al. 2023

Exploration of Targeted Anti-Tumor Therapy

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Macrophages, as ubiquitous and functionally diverse immune cells, play a central role in innate immunity and initiate adaptive immunity. Especially, tumor-associated macrophages (TAMs) are crucial contributors to the tumorigenesis and development of cancer. Thus, macrophages are emerging potential targets for cancer treatment. Among the numerous targeted therapeutic options, gene therapy is one of the most potential therapeutic strategies via directly and specifically regulating biological functions of macrophages at the gene level for cancer treatment. This short review briefly introduces the characteristics of macrophage populations, the functions of TAM in the occurrence, and the progress of cancer. It also summarized some representative examples to highlight the current progress in TAM-targeted gene therapy. The review hopes to provide new insights into macrophage-targeted gene therapy for precision cancer therapy.

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“… 18 As a result, many strategies to target or express IL-12 selectively in the tumor tissue are being pursued preclinically, as well as in clinical trials. 19 Engineering T cells with IL-12 is highly efficacious in mouse models 20 but results in serious adverse events in clinical settings. 14 In contrast, IL-18 is a myeloid-derived cytokine that elicits IFN-γ expression on T and NK lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Novel strategies exploiting interleukin-12 in cancer immunotherapy

Cited by 72 publications

References 132 publications

Immunotherapy with IL12 and PD1/CTLA4 inhibition is effective in advanced ovarian cancer and associates with reversal of myeloid cell-induced immunosuppression

Immunotherapy with IL12 and PD1/CTLA4 inhibition is effective in advanced ovarian cancer and associates with reversal of myeloid cell-induced immunosuppression

Macrophages as potential targets in gene therapy for cancer treatment

mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy

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