IL15 (Interleukin 15)

Incorporating the nanoconjugate prior to immunological treatment primarily reduced the population of suppressor cells. The most effective treatment was observed in two cases: as a result of immunotherapy including the use of a two-component vaccine DC/IL-12/TAg + DC/IL-18/TAg (TGI 62.3%) or after administration of HES-MTX nanoconjugate followed by immunotherapy with three-component vaccine - DC/IL-12/TAg + DC/IL-15/IL-15Rα/TAg + DC/IL-18/TAg (TGI 59.1%).

NK cells activated with IL-12/IL-15, and IL-12/IL-15/IL-18 co-cultured with MHC- tumor cells, and in each cytokine combination with MHC+ tumor cells caused proliferation inhibition and lysis of tumor cells. Activation of NK cells, particularly with the combination of IL-12/IL-15/IL-18 cytokines, shows potential clinical relevance in adoptive cell therapy.

P1/2, N=9, Terminated, Radboud University Medical Center | N=23 --> 9 | Trial completion date: Sep 2025 --> Jan 2026 | Recruiting --> Terminated | Trial primary completion date: Sep 2025 --> Jan 2026; Stop funding

Serum profiling of selected cytokines may provide biologically relevant information and support further investigation of inflammation-associated immune patterns in CD and CRC. Further studies are warranted to validate their clinical utility and to elucidate their mechanistic role in inflammation-driven colorectal carcinogenesis.

Exercise primes DLI and γδ T-cell products for enhanced responsiveness to TIGIT checkpoint inhibition. Targeting TIGIT likely augments DNAM-1 dependent cytotoxicity and improves anti-leukemic activity, supporting the integration of exercise-enhanced DLI and γδ T-cell therapies with immune checkpoint blockade as a safe strategy to improve relapse control in leukemia.

Notably, CAR-T cells exhibited synergistic antitumor responses when combined with TIGIT blockade, whereas CAR-NKT cells showed greater sensitivity to CD96 blockade in vivo. These findings highlight the divergent therapeutic dynamics of CAR-T and CAR-NKT cells and provide mechanistic insights that inform the rational design of next-generation cell therapies and combinatorial strategies for solid tumors.

Intermediate-risk patients could benefit from either intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) instillation, with emerging therapies such as UGN-102 chemoablation showing promise...Moreover, alternative agents such as sequential gemcitabine and docetaxel instillation have demonstrated favorable outcomes in both BCG-naïve and BCG-unresponsive patients...Gene therapy (nadofaragene firadenovec), oncolytic viral therapy (CG0070), interleukin-15 superagonist (Nogapendekin alfa-inbakicept), and innovative drug delivery systems (TAR-200) have shown encouraging clinical potential in this population. This review provides an overview of current intravesical treatment strategies for NMIBC across different risk groups and highlights promising new approaches aimed at overcoming the limitations of BCG therapy.

HCW9206, a first-in-class cytokine scaffold-based platform, enables production of more potent CAR T cell-based immunotherapies by generating a CAR T cell population, which is highly functional and also markedly enriched for long-lived TSCM cells. This strategy is broadly applicable to increase persistence and functionality of CAR T cells, enhancing their efficacy for treating infectious disease and cancer.

These data provide a rationale for the combination of lenalidomide with IL-2 family of cytokines to enhance the effectiveness of NK cells.

A previous study showed that IL-15 superagonist complex (N-803) enhanced ADCC activity mediated by NEO-201 in vitro against several human carcinoma cells, by modulating NK cells activation and cytotoxicity. In this study we demonstrated that IL-15 enhanced ADCC mediated by NEO-201 in vitro against human endometrial and ovarian cancer cell lines expressing NEO-201 target antigen, and that the combination of IL-15 and NEO-201, using purified human NK cells as effectors, had a modest effect in prolonging the survival of mice bearing human ovarian cancer, compared to IL-15 or NEO-201 alone. The ability of IL-15 to enhance NEO-201 efficacy, with NK cells as effectors, supports the hypothesis of combining NEO-201 and IL-15 with NK cell therapy (i.e. IL-15-secreting CAR-NK cells with a longer IL-15 in vivo half-life and stronger NK activity) for the treatment of gynecological cancers expressing O-glycans recognized by NEO-201.

It critically analyzes the advantages and limitations of different application strategies and explores their potential to overcome solid tumor treatment bottlenecks while improving CAR-T therapy safety and efficacy. These insights aim to inform basic research and clinical translation in this field.

Furthermore, these delivery systems are designed to respond to both intrinsic and extrinsic stimuli, enabling spatial and temporal control over cytokine activity. By synthesizing current progress and remaining challenges, this review outlines the future trajectory of cytokine-based therapeutics in achieving precise and safe anti-tumor immunity.