WO-2026096383-A1 - COMPOSITIONS AND METHODS FOR INDUCING PHAGOCYTOSIS

Abstract

Compositions and methods that are useful for inducing phagocytosis of a cancer cell and/or increasing killing of a cancer cell (e.g., by an immune cell) by contacting the cancer cell with an antibody capable of selectively binding to a CD43 protein expressed on the surface of cancer cells. In various embodiments, the CD43 protein is not expressed on the surface of a healthy cell.

Inventors

• GOLUB, TODD
• MANGUSO, Robert
• VALLURUPALLI, Mounica
• CHUNG, Jooho
• YATES, Kathleen

Assignees

• THE BROAD INSTITUTE, INC.
• THE GENERAL HOSPITAL CORPORATION
• DANA-FARBER CANCER INSTITUTE, INC.

Dates

Publication Date

20260507

Application Date

20251027

Priority Date

20241028

Claims (20)

1. 1. A method for increasing phagocytosis and/or killing of a cancer cell by an immune cell, the method comprising contacting the cancer cell with an antibody that selectively binds to a CD43 protein expressed on the surface of the cancer cell.
2. 2. The method of claim 1, wherein the cancer cell is a myeloma cell or a lymphoma cell.
3. 3. The method of claim 1, wherein the cancer cell is a leukemia cell.
4. 4. The method of claim 1, wherein the phagocytosis is macrophage-mediated phagocytosis.
5. 5. The method of claim 1, wherein the antibody selectively binds a glycoform of CD43 expressed on the surface of the cancer cell.
6. 6. The method of claim 1, wherein the antibody is a VHH antibody.
7. 7. The method of claim 1, wherein the immune cell is a natural killer (NK) cell or a T cell.
8. 8. The method of claim 1, wherein the immune cell is a macrophage.
9. 9. A method for increasing cancer cell phagocytosis and/or killing by immune cells in a subject in need thereof, the method comprising: administering to the subject an antibody that selectively binds to a CD43 protein expressed on the surface of a cancer cell, wherein the cancer cell is characterized as expressing CD43, thereby increasing phagocytosis of the cancer cell.
10. 10. The method of claim 9, wherein the cancer cell is a myeloma cell or a lymphoma cell.
11. 11. The method of claim 9, wherein the cancer cell is a leukemia cell.
12. 12. The method of claim 9, wherein the phagocytosis is macrophage-mediated phagocytosis. Atorney Docket No.: 167741-053601/PCT Electronic Deposit Date: October 27, 2025
13. 13. The method of claim 9, wherein the antibody selectively binds a glycoform of CD43 expressed on the surface of the cancer cell.
14. 14. The method of claim 9, wherein the antibody is a VHH antibody.
15. 15. The method of claim 9, wherein the immune cell is a natural killer (NK) cell or a T cell.
16. 16. The method of claim 9, wherein the immune cell is a macrophage.
17. 17. A method for treating a CD43-positive cancer in a selected subject, the method comprising: administering to the subject an antibody that selectively binds to a CD43 protein expressed on the surface of a cancer cell, wherein the subject is selected as having a cancer expressing CD43, thereby treating cancer in the subject.
18. 18. A kit comprising an antibody that selectively binds to a CD43 protein expressed on the surface of a cancer cell and instructions for using said antibody in the method of any one of claims 1-17.
19. 19. A method for identification of genes modulating phagocytosis of a cell by a macrophage, the method comprising: a) editing a cell to knock-out expression of a gene and yield an edited cell, b) co-culturing the cell with macrophages to yield a co-culture, and c) using nucleotide sequencing to determine whether the edited cell is enriched or depleted in a macrophage fraction of the co-culture, wherein enrichment or depletion of the edited cell in the macrophage fraction relative to a reference cell identifies the gene as modulating phagocytosis.
20. 20. The method of claim 19, wherein the nucleotide sequencing is single-cell sequencing.

Description

Atorney Docket No.: 167741-053601/PCT Electronic Deposit Date: October 27, 2025 COMPOSITIONS AND METHODS FOR INDUCING PHAGOCYTOSIS CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to and the benefit of U.S. Provisional Application No. 63/712,752, filed October 28, 2024, the entire contents of which are incorporated herein by reference. STATEMENT OF RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH This invention was made with government support under Grants No. CA242457, CA009172, and HL116324 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND During the past few decades, research has provided breakthroughs that have enhanced our understanding of the mechanisms and pathways that regulate the immune system’s response to cancer. However, despite these advances, obstacles still exist for the field of cancer immunotherapy. These include, among other things, the inability to predict treatment efficacy and patient response; the need for additional biomarkers; the development of resistance to cancer immunotherapies; the lack of clinical study designs that are optimized to determine efficacy; and high treatment costs. Thus, there is a present need for improved immunotherapies. SUMMARY As described below, the present disclosure features compositions and methods that are useful for inducing phagocytosis and/or increasing killing (e.g., by an immune cell) of a cancer cell by contacting the cancer cell with an antibody capable of selectively binding to a CD43 protein expressed on the surface of cancer cells. In various embodiments, the CD43 protein is not expressed on the surface of a healthy cell. In one aspect, the disclosure provides a method for increasing phagocytosis and/or killing of a cancer cell by an immune cell. The method involves contacting the cancer cell with an antibody that selectively binds to a CD43 protein expressed on the surface of the cancer cell. In another aspect, the disclosure provides a method for increasing cancer cell phagocytosis and/or killing by immune cells in a subject in need thereof. The method involves Atorney Docket No.: 167741-053601/PCT Electronic Deposit Date: October 27, 2025 administering to the subject an antibody that selectively binds to a CD43 protein expressed on the surface of a cancer cell, thereby increasing phagocytosis of the cancer cell. The cancer cell is characterized as expressing CD43. In another aspect, the disclosure provides a method for treating a CD43-positive cancer in a selected subject. The method involves administering to the subject an antibody that selectively binds to a CD43 protein expressed on the surface of a cancer cell, thereby treating cancer in the subject. The subject is selected as having a cancer expressing CD43. In another aspect, the disclosure provides a kit containing an antibody that selectively binds to a CD43 protein expressed on the surface of a cancer cell and instructions for using the antibody in the method of any aspect of the disclosure, or embodiments thereof. In another aspect, the disclosure provides a method for identification of genes modulating phagocytosis of a cell by a macrophage. The method involves a) editing a cell to knock-out expression of a gene and yield an edited cell. The method also involves b) co-culturing the cell with macrophages to yield a co-culture. The method further involves c) using nucleotide sequencing to determine whether the edited cell is enriched or depleted in a macrophage fraction of the co-culture. Enrichment or depletion of the edited cell in the macrophage fraction relative to a reference cell identifies the gene as modulating phagocytosis. In any aspect of the disclosure, or embodiments thereof, the cancer cell is a myeloma cell. In any aspect of the disclosure, or embodiments thereof, the cancer cell is a lymphoma cell. In any aspect of the disclosure, or embodiments thereof, the cancer cell expresses CD43. In any aspect of the disclosure, or embodiments thereof, the cancer cell is a leukemia cell. In any aspect of the disclosure, or embodiments thereof, the phagocytosis is macrophage- mediated phagocytosis. In any aspect of the disclosure, or embodiments thereof, the antibody selectively binds a glycoform of CD43 expressed on the surface of the cancer cell. In any aspect of the disclosure, or embodiments thereof, the antibody is a VHH antibody. In any aspect of the disclosure, or embodiments thereof, the nucleotide sequencing is single-cell sequencing. In any aspect of the disclosure, or embodiments thereof, expression of the gene is knocked out using CRISPR. In any aspect of the disclosure, or embodiments thereof, the method involves contacting the cell with a library of single guide RNAs (sgRNAs), where each sgRNA targets a unique gene for knock-out. In any aspect of the disclosure, or embodiments thereof, the cells express a polynucleotide programmable endonuclease. Atorney Docket No.: 16