Methods of activating lymphocyte cells and treating cancer and infectious conditions using same
A technology for lymphocyte and bacterial infection, applied in chemical instruments and methods, animal cells, organic active ingredients, etc., can solve problems such as failure to prove clinical benefits
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[0119] In the present invention, the term "cytokine" refers to an immune activating cytokine that can be used to activate any of the therapeutic lymphocytic cells described herein for use in the method, including substantially pure NK cells, and including Those isolated from peripheral blood mononuclear cells. According to an exemplary embodiment of the present invention, IL-2, IL-15, IL-21, Flt3-L, SCF, IL-7, IL-12 or IL18 may be used as such cytokines alone or in combination. In particular, since IL-2, IL-15, or IL-21 is known as a cytokine having an excellent role in the differentiation of peripheral blood mononuclear cells into NK cells and the proliferation of NK cells, it is desirable to use one of these cytokines. one or more combinations. According to an exemplary embodiment of the present invention, IL-2 is used, but the present invention is not limited thereto. Embodiments of the method additionally include IL-2 agonists, IL-2 homologues, or other synthetic, optimi...
Embodiment 1
[0251] Options for treating cancer patients and viral infections including HIV
[0252] As a first step, NK cells are obtained or purified from any suitable commercial source - and the cells are allogeneic, as described herein and in the sections above.
[0253] As described herein, there are four different infusion options for administering therapeutic cellular compositions to patients. These therapeutic cellular compositions include the following cellular components:
[0254] Activate NK cells; or
[0255] Activated NK cells + activated GDT cells; or
[0256] Activated NK cells + activated GDT cells + iNKT cells; or
[0257] Activate NK cells+CD3 T cells.
[0258] Phase 1: Patient Preparation Options
[0259] Depending on the patient's condition and disease stage, such as figure 1 Patients were pretreated with one of the following conditioning regimens listed in Tables 1-5, as described. Day 0 reference is the day of the infusion (eg, infusion of the activated lymphoc...
Embodiment 2
[0311] Immune checkpoint inhibitors administered after activated lymphocyte therapy
[0312] In certain embodiments, the patient is treated with one of the lymphocyte-activating regimens described herein, followed by further administration of an immune checkpoint inhibitor within a time frame of 4-14 days after administration of the lymphocyte-activating composition. While not wishing to be bound by theory, it is believed that since donor activated lymphocytic cells live approximately 4 / 5-15 days in recipient patients, they function to present tumor antigens when they begin to die, And act as a vaccine in patients. At this point (approximately 4-14 days after administration of the activated lymphocytic cells), the patient may be administered either or a combination of two immune cell checkpoint inhibitors, such as molecules that send suppressive signals to the immune system. Following administration of immune cell checkpoint inhibitors, postconditioning treatment options as d...
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