IL15

Overview

Interleukin-15 (IL15) is a pleiotropic cytokine that plays a critical role in promoting survival, proliferation, and effector differentiation of lymphocytes, particularly T cells and natural killer (NK) cells. As a proinflammatory cytokine, IL15 is a key mediator of adaptive and innate immune responses, functioning through both autocrine and paracrine signaling pathways. In contemporary immunotherapeutic applications, IL15 has emerged as a strategic component in engineered cellular therapies, where its capacity to enhance immune cell fitness, proliferative capacity, and persistence has positioned it as a valuable augmentation factor in chimeric antigen receptor (CAR) T cell and CAR-NK cell platforms. The ability to deliver IL15 through multiple modalities—including direct cytokine co-expression, mRNA-based therapies, and gene transfer vectors—has expanded its therapeutic utility in treating hematologic and solid malignancies characterized by immunosuppressive tumor microenvironments.

Recent Publications Focus

Below is a summary of the newest research publications targeting IL15 (sorted by publication date).

• PMID: 42412320 — Plasma proteomics-based liquid biopsy for predicting efficacy of PD-1-based immunochemotherapy in advanced gastric cancer

  • This prospective cohort study used plasma proteomic profiling to evaluate biomarkers associated with response to PD-1-based immunochemotherapy in advanced gastric cancer.
  • The reported finding was that responders had significantly lower baseline IL-15 levels. This suggests that circulating IL15 may be associated with treatment response patterns in this clinical setting, although the publication context provided does not establish causality.

• PMID: 42387611 — Large language model-guided CAR-T in silico platform for cytokine optimization in liver cancer with low antigen density

  • This study used a large language model-guided in silico platform to optimize cytokine selection for cytokine-armored GPC3 CAR-T cells in liver cancer models with low antigen density.
  • Computational predictions identified IL-15 as the most effective enhancer, particularly against tumor cells with low GPC3 expression.
  • The work supports IL15 as a candidate cytokine for improving CAR-T performance in difficult-to-target tumors, especially where antigen density is limited.

• PMID: 42116169 — A novel mRNA-based multi-cytokine strategy to reprogram the peritoneal tumor microenvironment in ovarian cancer

  • This study investigated an mRNA-based immunotherapy delivered via lipid nanoparticles in a syngeneic ID8-Fluc ovarian cancer mouse model.
  • The therapeutic construct encoded a combination of single-chain interleukins and inflammatory mediators, including IL-12, IL-15, pro-IL-18, and CASP1.
  • The goal was to reprogram the immunosuppressive peritoneal tumor microenvironment. In this context, IL15 was part of a multi-cytokine strategy intended to enhance antitumor immunity in ovarian cancer.

• PMID: 41996826 — CAR-NK Cells in B-cell Lymphoma: A New Frontier toward Accessible and Scalable Cellular Therapy

  • This review or clinical discussion highlighted TAK-007, an off-the-shelf allogeneic CD19 CAR NK-cell therapy that expresses IL-15.
  • In the cited phase II study, the therapy showed encouraging response rates, rapid availability, and an excellent safety profile in heavily pretreated B-cell lymphoma, including patients previously treated with CAR-T therapy, though durability remained limited.
  • IL15 is presented here as a key engineering feature supporting NK-cell fitness and therapeutic activity.

• PMID: 41928453 — Sialic acid cis-ligand dynamics modulate Siglec-7 and -9 function and affect Siglec-7/9 co-blockade to potentiate natural killer cell anti-tumor activity

  • This study examined how Siglec-7 and -9 cis-ligand dynamics influence NK-cell function and the effects of Siglec-7/9 co-blockade.
  • In primary human NK cells, activation with IL-15/IL-2-induced proliferation was associated with significant downregulation of Siglec-7 and -9 cis-ligand expression.
  • The findings place IL15 within a broader NK-cell activation framework, where it contributes to phenotypic changes linked to enhanced antitumor activity.

• PMID: 41922262 — Effects of Janus kinase inhibition and interleukin 6 inhibition on serum cytokine/chemokine in idiopathic multicentric Castleman disease

  • This translational analysis compared cytokine responses under filgotinib and tocilizumab treatment in idiopathic multicentric Castleman disease.
  • Among the cytokines with differential responses, IL-15 showed greater suppression with filgotinib.
  • The study indicates that IL15 can be modulated in inflammatory disease settings and may serve as part of the cytokine readout for therapeutic pathway effects.

• PMID: 41860794 — Coexpression of IL15 Promotes Effector Differentiation and Sustained Proliferative Capacity in ALPPL2-Specific Human CAR T Cells

  • This study focused on ALPPL2-specific human CAR T cells and examined the effect of coexpression of IL15.
  • The publication context states that IL15 promotes T-cell survival and fitness and may improve expansion and persistence of CAR T cells.
  • The reported conclusion was that IL15 coexpression promotes effector differentiation and sustained proliferative capacity, supporting its use as an engineering strategy to strengthen CAR T-cell products.

• PMID: 41538301 — exercise-mobilized lymphocytes enhance the function of cytokine-induced memory-like NK cells against myeloid leukemia

  • This study addressed cytokine-induced memory-like (CIML) NK cells, generated by short-term activation with IL-12, IL-15, and IL-18.
  • The resulting CIML NK cells were described as having enhanced antitumor activity, proliferation, and persistence after adoptive transfer.
  • IL15 is therefore part of a cytokine priming regimen used to generate NK cells with memory-like properties relevant to leukemia immunotherapy.

• PMID: 41917051 — Miniature and versatile genome regulation TnpB-ωRNA toolkits facilitate cancer immunotherapy

  • This study used AAV-ImmunAct, a genome regulation toolkit, to activate immune-related genes including CXCL9, IL-15, and IFN-γ.
  • The context suggests IL15 was targeted as part of a gene activation strategy intended to support cancer immunotherapy.
  • The publication highlights IL15 as a transcriptional target in engineered immune-modulatory platforms rather than as a direct protein therapy.

Overall, these recent publications show IL15 being used in several complementary ways: as an engineered payload in CAR-T and CAR-NK cells, as a component of multi-cytokine mRNA therapies, as a priming factor for NK-cell activation, and as a biomarker-associated cytokine in translational studies. Across these settings, IL15 is consistently linked to lymphocyte survival, proliferation, persistence, and antitumor immune function.

Background PMIDs

• [PMID 41538301]
• [PMID 41928453]

Result PMIDs

• [PMID 41922262]

Target PMIDs

• [PMID 42387611]
• [PMID 41860794]
• [PMID 42116169]
• [PMID 41996826]
• [PMID 41917051]
• [PMID 42412320]