Compositions and Methods for Cancer Immunotherapy

Abstract

The invention provides compositions and improved methods for the treatment of cancer using IL-2 immunotherapy. The methods of the invention comprise administering to a patient, the fusion protein of SEQ ID NO: 1 at a dose of about 6 μg / kg / day to about 70 μg / kg / day and preferably at a dose of at least about 6 μg / kg / day to about 15 μg / kg / day or at a corresponding fixed per day dose based, for example, on an average about 60 to about 70 kg adult human or based, for example, on a child of about 12 kg to about 50 kg or more, wherein administration results in a dose dependent increase in circulating NK cells and CD8+ cells in a patient in the absence of a dose dependent increase in circulating immunosuppressive T regulatory (Treg) cells and preferably wherein the increase in circulating NK cells and CD8+ cells is greater relative to the increase in circulating T Treg cells.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 860,182, filed on Jun. 11, 2019; 62 / 932,160, filed on Nov. 7, 2019 and 62 / 924,356, filed on Oct. 22, 2019. The entire teachings of the above applications are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]Interleukin-2 (IL-2) is a cytokine that induces proliferation of antigen-activated T cells and stimulates natural killer (NK) cells. The biological activity of IL-2 is mediated through a multi-subunit IL-2 receptor complex (IL-2R) of three polypeptide subunits that span the cell membrane: p55 (IL-2Rα, the alpha subunit, also known as CD25 in humans), p75 (IL-2R13, the beta subunit, also known as CD122 in humans) and p64 (IL-2Rγ, the gamma subunit, also known as CD132 in humans). T cell response to IL-2 depends on a variety of factors, including: (1) the concentration of IL-2; (2) the number of IL-2R molecules on the cell surface; and (3) the number of IL-2R occupi...

AI Technical Summary

Benefits of technology

The invention provides a new method for treating cancer using a fusion protein called SEQ ID NO:1. This method involves administering the fusion protein at a dose of 6 μg / kg / day to 15 μg / kg / day for 1 to 5 consecutive or non-consecutive days, followed by a rest period of at least 9 consecutive days. This treatment results in a dose-dependent increase in circulating NK cells and CD8+ cells in a patient, without an increase in circulating T regulatory (Treg) cells. Compared to high dose recombinant human IL-2 (rhlIL-2) treatment, the new method has improved safety and lower risk of side effects, such as capillary leak syndrome and cytokine release syndrome. The patient also has a lower risk of Treg-related diseases. The method is effective in treating cancer in a patient and results in better outcomes compared to rhlIL-2 treatment.

Problems solved by technology

Outcomes of systemic IL-2 administration in cancer patients are poor.

While 15 to 20 percent of patients respond objectively to high-dose IL-2, the great majority do not, and many suffer severe, life-threatening side effects.

It has been hypothesized that a contributing factor limiting the therapeutic efficacy of rhIL-2 is that it preferentially activates and induces the expansion of immunosuppressive CD4+ Tregs, which can counteract anticancer immune responses.

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