WO-2026095044-A1 - ENHANCEMENT OF GRAFT-VERSUS-TUMOR EFFECT USING ROPEGINTERFERON

Abstract

The present invention simultaneously achieves, in allogeneic hematopoietic cell transplantation as a treatment for blood cancer, enhancement of a graft-versus-tumor effect (GVT effect) and/or a graft-versus-leucocyte effect (GVL effect) and suppression of graft-versus-host disease (GVHD).　The present invention relates to a pharmaceutical composition which is for enhancement of a GVL and/or GVT effect in a hematopoietic cell transplantation treatment and which comprises ropeginterferon.

Inventors

• TESHIMA, TAKANORI
• HASHIMOTO, Daigo
• TAZAWA SAITO, Yumika

Assignees

• 国立大学法人北海道大学

Dates

Publication Date

20260507

Application Date

20251031

Priority Date

20241101

Claims (9)

1. A pharmaceutical composition containing lopeg interferon for enhancing the effects of GVL and/or GVT in hematopoietic stem cell transplantation therapy.
2. The pharmaceutical composition according to claim 1, characterized by reducing hematopoietic stem cells.
3. Furthermore, the pharmaceutical composition according to claim 1 is characterized by having a GVHD inhibitory effect.
4. A pharmaceutical composition according to claim 1 for preventing and/or treating the recurrence of leukemia.
5. The pharmaceutical composition according to claim 4, wherein the leukemia is acute myeloid leukemia.
6. The pharmaceutical composition according to claim 1, wherein the hematopoietic cells are bone marrow.
7. The pharmaceutical composition according to claim 1, wherein the hematopoietic cells are T cells.
8. The pharmaceutical composition according to claim 1, further characterized by containing hematopoietic stem cell grafts.
9. The pharmaceutical composition according to claim 1 or 8, wherein lopeg interferon is lopeg interferon α-2b.

Description

Enhancement of graft-versus-tumor effect using LOPEG interferon This patent application claims priority and interest under the Paris Convention and priority under Article 41 of the Japanese Patent Act, based on Japanese Patent Application No. 2024-193170 (filed November 1, 2024), and by reference herein, the entire contents of the said application are incorporated herein by reference. This invention belongs to the field of hematopoietic stem cell transplantation therapy. More specifically, this invention relates to a pharmaceutical composition for enhancing the GVL/GVT effect in hematopoietic stem cell transplantation therapy, and more precisely, to a pharmaceutical composition containing lopeg interferon for enhancing the GVL/GVT effect in hematopoietic stem cell transplantation therapy. Allogeneic hematopoietic stem cell transplantation is used as a treatment method for blood cancers such as leukemia. This method relies on the graft-versus-tumor effect (GVT effect), in which immune cells, mainly lymphocytes such as T cells, contained in donor-derived hematopoietic cells attack tumor cells remaining in the recipient's (patient's) body, leading to the cure or control of the underlying disease. The GVT effect is expected to suppress recurrence and ultimately lead to a complete cure by continuously attacking and eliminating tumor cells through the immune response. On the other hand, graft-versus-host disease (GVHD) is known as an immune response in which transplanted donor-derived lymphocytes recognize the patient's normal body parts, such as the skin, liver, lungs, and intestines, as foreign bodies and attack them. In other words, GVT and GVHD are two sides of the same coin, and if GVHD is suppressed too much by immunosuppressive therapy, the GVT effect, which is an important immunotherapeutic effect for achieving a cure, may be canceled out as a result. Therefore, in treatments that aim to induce the GVT effect, the development of GVHD as a side effect and recurrence after transplantation are problematic. Tumor recurrence after transplantation is the most common cause of death after transplantation, and separating GVHD from the GVT effect is the ultimate goal in the field of transplantation (Non-Patent Literature 7). To enhance the graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia (AML), maintenance therapies such as hypomethylating agents and FLT3 inhibitors have been developed. These prevent immune evasion by leukemia cells or suppress donor T cell fatigue. However, leukemia recurrence after transplantation remains a significant problem (Non-Patent Documents 1, 2, and 3). In addition, it is known that endogenous interferon suppresses GVHD and that interferon administration enhances the GVT effect, in relation to the problems of GVHD development and recurrence after transplantation (Non-Patent Documents 4 and 5). Furthermore, it has been suggested that lopeg interferon α-2b, described in Patent Document 1, shows a higher therapeutic effect than interferon against acute lymphoblastic leukemia (ALL) (Non-Patent Document 6). Figure 1 shows an experimental scheme to investigate the effect of Ropeg interferon α-2b (RopegIFN) administration on the GVL effect. In the figure, "MLL-AF9 cells" refers to AML cells created by introducing the KMT2A::MLLT3 fusion gene, "TCD-BM" refers to T cell-depleted bone marrow, and "AML" refers to acute myeloid leukemia.Figure 2 shows the enhancing effect of RopegIFN on the GVL effect. Figure 2A is a graph showing the changes in peripheral blood AML cell ratio for the TCD-BM + Vehicle administration group (no GVL effect), the TCD-BM + RopegIFN administration group (no GVL effect), the TCD-BM + T cell + Vehicle administration group (GVL effect present), and the TCD-BM + T cell + RopegIFN administration group (GVL effect present). Figure 2B is a graph showing the overall survival rate (Overall survival %) for each group.Figure 3 is a graph showing the results of flow cytometry analysis of the effects of RopegIFN on AML cells. rmIFN-α is recombinant mouse IFN-α.Figure 4 shows that administration of RopegIFN and IFNα enhances the expression of MHC class I in leukemia cells and leukemia stem cells (LSCs). Figure 4A is a representative flow cytometry histogram of leukemia cells, and Figure 4B shows the change in the intensity of MHC class I expression on leukemia cells and LSCs from the vehicle administration group.Figure 5 shows that administration of RopegIFN and IFNα enhances the expression of MHC class II in leukemia cells and LSCs. Figure 5A is a representative flow cytometry histogram of leukemia cells, and Figure 5B shows the change in the intensity of MHC class II expression on leukemia cells and LSCs from the vehicle administration group.Figure 6 shows that administration of RopegIFN and IFNα enhances the expression of TRAIL-R2 (a T cell target) on leukemia cells and LSCs. Figure 6A is a representative flow cyto