Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model

Near infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that employs a monoclonal antibody (mAb) conjugated to a photo-absorber dye, IRDye700DX, which is activated by 690 nm light. Cancer cell-targeted NIR-PIT induces rapid necrotic/immunogenic cell death (ICD) that induces antitumor host immunity including re-priming and proliferation of T cells. Interleukin-15 (IL-15) is a cytokine that activates natural killer (NK)-, B- and T-cells while having minimal effect on regulatory T cells (Tregs) that lack the IL-15 receptor. Here, we hypothesized that IL-15 administration with cancer cell-targeted NIR-PIT could further inhibit tumor growth by increasing antitumor host immunity. Three syngeneic mouse tumor models, MC38-luc, LL/2, and MOC1, underwent combined CD44-targeted NIR-PIT and short-term IL-15 administration with appropriate controls. Comparing with the single-agent therapy, the combination therapy of IL-15 after NIR-PIT inhibited tumor growth, prolonged survival, and increased tumor infiltrating CD8+ T cells more efficiently in tumor-bearing mice. IL-15 appears to enhance the therapeutic effect of cancer-targeted NIR-PIT.

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Combining synthetic carbohydrate vaccines with cancer cell glycoengineering for effective cancer immunotherapy

Cancer Immunology Immunotherapy ◽

10.1007/s00262-012-1224-6 ◽

2012 ◽

Vol 61 (11) ◽

pp. 2045-2054 ◽

Cited By ~ 14

Author(s):

Lei Qiu ◽

Xi Gong ◽

Qianli Wang ◽

Jie Li ◽

Honggang Hu ◽

...

Keyword(s):

Cancer Immunotherapy ◽

Cancer Cell ◽

Synthetic Carbohydrate ◽

Carbohydrate Vaccines

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A new mode of cancer cell death induced by hyperthermia and non specific (macrophagic) cancer immunotherapy: lysosomal exocytosis

Biomedicine & Pharmacotherapy ◽

10.1016/0753-3322(94)90180-5 ◽

1994 ◽

Vol 48 (7) ◽

pp. 331 ◽

Cited By ~ 5

Author(s):

P. Pontiggia ◽

G. Mathé

Keyword(s):

Cell Death ◽

Cancer Immunotherapy ◽

Cancer Cell ◽

Cancer Cell Death

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Tumor Cell-Intrinsic Immunometabolism and Precision Nutrition in Cancer Immunotherapy

Cancers ◽

10.3390/cancers12071757 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1757 ◽

Cited By ~ 1

Author(s):

Elisabet Cuyàs ◽

Sara Verdura ◽

Begoña Martin-Castillo ◽

Tomás Alarcón ◽

Ruth Lupu ◽

...

Keyword(s):

Tumor Cell ◽

Cancer Immunotherapy ◽

Tumor Cells ◽

Cancer Cell ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Acquired Resistance ◽

Dietary Interventions ◽

Metabolic Traits ◽

Review State

One of the greatest challenges in the cancer immunotherapy field is the need to biologically rationalize and broaden the clinical utility of immune checkpoint inhibitors (ICIs). The balance between metabolism and immune response has critical implications for overcoming the major weaknesses of ICIs, including their lack of universality and durability. The last decade has seen tremendous advances in understanding how the immune system’s ability to kill tumor cells requires the conspicuous metabolic specialization of T-cells. We have learned that cancer cell-associated metabolic activities trigger shifts in the abundance of some metabolites with immunosuppressory roles in the tumor microenvironment. Yet very little is known about the tumor cell-intrinsic metabolic traits that control the immune checkpoint contexture in cancer cells. Likewise, we lack a comprehensive understanding of how systemic metabolic perturbations in response to dietary interventions can reprogram the immune checkpoint landscape of tumor cells. We here review state-of-the-art molecular- and functional-level interrogation approaches to uncover how cell-autonomous metabolic traits and diet-mediated changes in nutrient availability and utilization might delineate new cancer cell-intrinsic metabolic dependencies of tumor immunogenicity. We propose that clinical monitoring and in-depth molecular evaluation of the cancer cell-intrinsic metabolic traits involved in primary, adaptive, and acquired resistance to cancer immunotherapy can provide the basis for improvements in therapeutic responses to ICIs. Overall, these approaches might guide the use of metabolic therapeutics and dietary approaches as novel strategies to broaden the spectrum of cancer patients and indications that can be effectively treated with ICI-based cancer immunotherapy.

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Blood Concentrations of Interleukin-15 in Cancer Patients and Their Variations during Interleukin-2 Immunotherapy: Preliminary Considerations

The International Journal of Biological Markers ◽

10.1177/172460089801300309 ◽

1998 ◽

Vol 13 (3) ◽

pp. 169-171 ◽

Cited By ~ 4

Author(s):

P. Lissoni ◽

F. Rovelli ◽

M. Mandalà ◽

S. Barni

Keyword(s):

Cancer Immunotherapy ◽

Cancer Patients ◽

Metastatic Cancer ◽

Cell Cancer ◽

Interleukin 2 ◽

Serum Levels ◽

Control Group ◽

Blood Concentrations ◽

Significant Difference ◽

Interleukin 15

In addition to the better known cytokines IL-2 and IL-12, IL-15, which is mainly produced by macrophages, is a new antitumor cytokine with a mechanism of action similar to that of IL-2. At present, however, there are no data about IL-15 secretion in cancer patients. This study was carried out to evaluate IL-15 blood concentrations in patients with early or advanced cancer and their possible variations in response to IL-2 cancer immunotherapy. The study included 40 patients with solid tumors, 24 of whom had metastatic disease. In addition, IL-15 secretion was evaluated during subcutaneous low-dose IL-2 therapy (6 million IU/day for 6 days/week for 4 weeks) in 14 metastatic renal cell cancer patients by collecting blood samples at weekly intervals. The control group consisted of 40 age-matched healthy subjects. Serum levels of IL-15 were measured by an enzyme immunoassay. No significant difference in mean serum levels of IL-15 was observed between cancer patients and controls. Moreover, the mean serum levels of IL-15 found in metastatic cancer patients were not significantly different from those found in patients with limited disease. Finally, no significant changes in mean levels of IL-15 occurred during IL-2 cancer immunotherapy. This preliminary study would suggest that IL-15 secretion is substantially within the normal range in cancer patients, both in early and advanced disease, and no variation seems to occur in response to IL-2 administration.

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