AbstractCancer immunotherapy utilizes our immune system to attack cancer cells and is an extremely promising strategy for cancer treatment. Although immune-checkpoint blockade, such as anti-PD-1 (programmed cell death 1) antibody, has demonstrated significant enhancement of anti-tumor immunity and has induced notable clinical outcomes, its response rates remain low, and adverse effects are always a matter of concern; therefore, new targets for cancer immunotherapy are always desired. In this situation, new concepts are needed to fuel the investigation of new target molecules for cancer immunotherapy. We propose that CD69 is one such target molecule. CD69 is known to be an activation marker of leukocytes and is also considered a crucial regulator of various immune responses through its interacting proteins. CD69 promotes T-cell retention in lymphoid tissues via sphingosine-1-phosphate receptor 1 (S1P1) internalization and also plays roles in the pathogenesis of inflammatory disorders through interacting with its functional ligands Myl9/12 (myosin light chains 9, 12a and 12b). In anti-tumor immunity, CD69 is known to be expressed on T cells in the tumor microenvironment (TME) and tumor-draining lymph nodes (TDLNs). We revealed that CD69 negatively regulates the effector function of intratumoral T cells and importantly controls the ‘exhaustion’ of CD8 T cells. In addition, we and others showed that either CD69 deficiency or the administration of anti-CD69 monoclonal antibody enhances anti-tumor immunity. Thus, CD69 is an attractive target for cancer immunotherapy.

01 Oct 2019·Journal of VirologyQ2 · MEDICINE

CD69 Targeting Enhances Anti-vaccinia Virus Immunity

Q2 · MEDICINE

Article

Author: Lauzurica, Pilar ; Lopez, Daniel ; Sabio, Guadalupe ; Redondo-Antón, Jennifer ; Albentosa, Almudena ; Notario, Laura ; Leiva, Magdalena ; Alari-Pahissa, Elisenda

In this study, we demonstrate the influence of human and mouse anti-CD69 therapies on the immune response to VACV infection. We report that targeting CD69 increases the leukocyte numbers in the secondary lymphoid organs during infection and improves the capacity to clear the viral infection. Targeting CD69 increases the numbers of gamma interferon (IFN-γ)- and tumor necrosis factor alpha (TNF-α)-producing NK and T cells. In mice expressing human CD69, treatment with an anti-CD69 MAb produces increases in cytokine production, survival, and proliferation mediated in part by mTOR signaling. These results, together with the fact that we have mainly worked with a human-CD69 transgenic model, reveal CD69 as a treatment target to enhance vaccine protectiveness.

30 Apr 2019·Journal of Nutritional Science and VitaminologyQ4 · MEDICINE

Effect of Cholecalciferol in Food Allergy Mouse Model Is Associated with Decrease of CD69<sup>+</sup> CD4<sup>+</sup> T Cells

Q4 · MEDICINE

Article

Author: YANAGISAWA, Naoko ; ZAIM, Ece ; OSAKA, Toshifumi ; YAGI, Junji ; ASHINO, Shigeru

Food allergy prevalence is increasing all over the world. Recent epidemiologic studies have shown the link between vitamin D₃ insufficiency and food allergy occurrence. In this study, we investigated the effect of supplementation with cholecalciferol, a widely used form of vitamin D₃, on food allergy using an experimental mouse model. In wild-type BALB/c mice which were sensitized and challenged with an experimental allergen, ovalbumin, a clinical symptom of food allergy, diarrhea, was significantly induced with the elevation of immunoglobulin E level and the increases of T helper 2 cytokine productions, such as interleukin-4, -5, and -13 (p<0.05), whereas no change in T helper 1 cytokine production, such as interferon-γ, was observed. It was also found that cell population of CD69⁺ CD4⁺ T cells was increased slightly in spleen and significantly in the mesenteric lymphnode with the diarrheal symptom (p<0.05). Treatment of cholecalciferol reduced the allergic diarrhea (p<0.05) with the decreasing tendency of CD69⁺ CD4⁺ T cells, suggesting that the cell population might be associated with the attenuating effect of cholecalciferol on diarrhea occurrence, although immunoglobulin E levels and cytokine productions were not significantly altered by the treatment of cholecalciferol. When given the mice anti-CD69 mAb treatment, significant improvement of allergic diarrhea symptom was observed (p<0.05), accompanying the decrease of CD69⁺ CD4⁺ T cells which suggested the contribution of these cells to the diarrhea symptom. Taken together, we suggest that administration of cholecalciferol might be useful to suppress symptomatic food allergy in association with the decrease of CD69⁺ CD4⁺ T cells.

100 Deals associated with GFC-101

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Indication	Highest Phase	Country/Location	Organization	Date
Irritable Bowel Syndrome	Preclinical	JP	GeneFrontier Corp.	-
Rheumatoid Arthritis	Preclinical	JP	GeneFrontier Corp.	-
Respiration Disorders	Discovery	JP	GeneFrontier Corp.	-

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